MolDX's New Coverage for Hereditary ATTR Amyloidosis Genetic Testing: What Labs Need to Know

Q: Can a lab bill for repeat or family-member testing?

Comprehensive TTR testing is limited to one test per patient. Testing a relative for a previously identified familial variant is billed as a separate patient encounter with its own medical necessity documentation, not as a repeat test on the original patient.

Q: Why does genetic confirmation matter more now than a few years ago?

Three FDA-approved therapies -- tafamidis, acoramidis (approved November 2024), and vutrisiran (expanded to ATTR cardiomyopathy in March 2025) -- require a confirmed ATTR diagnosis before a cardiologist will prescribe. Genetic testing that once mainly supported family counseling is now frequently the gating step for active treatment decisions.

ScreenMyGene Team·Published September 12, 2026·8 min read·Clinically reviewed by Dr. Ashraf, Ph.D.

Navy and teal editorial photograph of a molecular laboratory scientist handling genetic testing samples, symbolizing hereditary amyloidosis genetic testing

Short answer: Since August 2025, MolDX has rolled out new Local Coverage Determinations across Palmetto GBA, Novitas, First Coast, and CGS establishing Medicare coverage for molecular testing for hereditary transthyretin amyloidosis (hATTR). A billing update effective September 25, 2025 added CPT 81404 and locked coverage to one test per patient. Labs offering TTR gene sequencing need a current DEX Z-code, documented clinical or family-history criteria, and proof the result will change management — not just confirm suspicion.

What changed, and why it matters for labs now

Hereditary transthyretin amyloidosis is a progressive, autosomal-dominant disease caused by variants in the TTR gene, and until recently it was chronically underdiagnosed — patients with polyneuropathy or unexplained cardiomyopathy often cycled through cardiologists, neurologists, and rheumatologists for years before anyone ordered a TTR sequence. That changed on the payer side starting August 17, 2025, when Palmetto GBA finalized LCD L39935, "MolDX: Molecular Testing for Identification and Management of Hereditary Transthyretin Amyloidosis." Parallel LCDs and billing articles have since followed at Novitas, First Coast, and CGS (which revised its version as recently as September 3, 2026), meaning hATTR molecular testing now has an explicit, MolDX-defined coverage pathway across most MolDX jurisdictions rather than ad hoc claim-by-claim review.

The timing is not incidental. Three disease-modifying therapies — tafamidis (Vyndaqel), acoramidis (Attruby, FDA-approved November 2024), and vutrisiran (Amvuttra, with an expanded FDA approval for ATTR cardiomyopathy in March 2025) — now target ATTR-CM directly, and all of them require a confirmed diagnosis before a cardiologist will prescribe. A genetic test that used to be a nice-to-have for family counseling is now a gating step for expensive, disease-modifying treatment. CMS's coverage language follows that logic closely: testing has to be tied to a clinical decision, not curiosity.

hATTR is rare but severe, and testing sensitivity is high — the missing piece for years was a defined Medicare coverage pathway tying the test to treatment decisions.

What MolDX actually requires for coverage

LCD L39935 and its companion billing articles do not cover TTR sequencing simply because a clinician ordered it. Coverage requires meeting a specific clinical framework, and documentation that falls short of it is the most common reason these claims get denied:

A qualifying clinical picture. Either an existing clinical diagnosis of ATTR amyloidosis, or cardiac features suggestive of ATTR-cardiomyopathy paired with African ancestry, a first-degree relative with hATTR, or other suggestive findings, or progressive sensorimotor/autonomic neuropathy paired with a first-degree relative with hATTR or other suggestive features.
Documented genetic counseling. The patient must have been offered counseling about the test and what a positive or negative result would mean, before the sample is drawn.
Clinical utility, not curiosity. The result has to be positioned to change management — confirming eligibility for a TTR stabilizer or RNA-targeted therapy, guiding family cascade testing, or ruling out ATTR before a different amyloidosis workup.
A completed MolDX technical assessment on file for the specific test being billed, tied to a current DEX Z-code — the same registration requirement that underlies MolDX's broader molecular pathology policy.
Single-variant testing is allowed when a familial TTR variant has already been identified in the family, which matters for cascade testing of asymptomatic relatives.

Source: CMS Medicare Coverage Database, LCD L39935 (MolDX: Molecular Testing for Identification and Management of Hereditary Transthyretin Amyloidosis), Palmetto GBA.

None of this is unusual by MolDX standards, but hATTR's mixed presentation — cardiology, neurology, and GI symptoms can each dominate depending on the patient — means the clinical-indication documentation has to come from whichever specialist actually worked up the case, not a boilerplate order justification.

Coverage rolled out MAC by MAC rather than all at once — labs billing outside Palmetto's jurisdiction should confirm their own MAC has matching language before assuming reciprocity.

Billing specifics: codes, limits, and documentation

The companion billing and coding article (A59849), most recently revised September 25, 2025, added CPT 81404 to the codes payable under this policy and ties reimbursement to a current DEX Z-code identifying the specific assay. Two operational details trip labs up most often:

One test per patient, one unit of service. MolDX explicitly limits comprehensive TTR testing to a single billable instance per patient — repeat full-gene testing on the same person will not be separately reimbursed. Cascade testing for a known familial variant in a relative is a separate patient and a separate claim, not a repeat test on the proband.
ICD-10 coding has to match the clinical picture, not just "amyloidosis." The policy's supporting diagnosis codes span heredofamilial amyloidosis (E85.0–E85.4), polyneuropathy and other nerve disorders (G57.9x, G59, G60.3, G60.9), and cardiomyopathy (I42.0, I42.8, I43) — reflecting how differently hATTR can present. Coding to the specific presenting syndrome, and pairing it with the qualifying risk factor (ancestry or family history) in the chart, is what gets these claims through medical review on the first pass.

Labs should treat this the same way they treat any other MolDX-governed test prone to denial: the claim is only as strong as the ordering documentation behind it, and a technical assessment filed once at launch needs to stay current as the LCD is revised.

What labs, counselors, and cardiology/neurology practices should do now

Confirm your MAC has matching coverage. If you bill in a MolDX jurisdiction (Palmetto, Novitas, First Coast, CGS, Noridian, or WPS), check that jurisdiction's current LCD and billing article rather than assuming national uniformity — language and effective dates differ by contractor.
Standardize the pre-test documentation, not just the test order. Build the counseling attestation and the qualifying clinical/ancestry/family-history criteria into the requisition workflow so ordering clinicians aren't reconstructing it after a denial.
Flag cascade-testing cases separately. Once a familial variant is identified, downstream relative testing should be billed and documented as its own encounter with its own medical necessity, not bundled into the proband's file.
Loop in cardiology and neurology referral sources. With three approved therapies now tied to confirmed diagnosis, practices that haven't updated their amyloidosis workup pathways are likely still sending patients through imaging-heavy workups before genetics — a genetic counselor or lab liaison flagging this gap is a low-cost, high-value outreach.
Recheck your general Medicare coverage documentation against this specific LCD rather than relying on older, more generic guidance — hATTR's criteria are more specific than the baseline NCD 90.2 framework.
Keep a live reference on hand. Ordering teams and genetic counselors evaluating whether a patient's presentation clears this bar can start with a coverage and clinical-utility overview at ScreenMyGene before escalating to MAC-specific policy language.

Frequently asked questions

Is hATTR genetic testing covered by Medicare everywhere now?

Coverage is MolDX-driven and has rolled out MAC by MAC rather than as a single national policy. Palmetto GBA, Novitas, First Coast, and CGS have finalized or updated LCDs and billing articles for hATTR molecular testing as of 2025–2026; labs should verify the specific LCD in force for their own MAC rather than assume identical language everywhere.

What CPT code should labs use to bill hATTR molecular testing?

The MolDX billing and coding article for this policy added CPT 81404 in its September 25, 2025 revision. Claims also require a current DEX Z-code identifying the specific test, consistent with standard MolDX molecular pathology billing requirements.

Can a lab bill for repeat or family-member testing?

Comprehensive TTR testing is limited to one test per patient. Testing a relative for a previously identified familial variant is billed as a separate patient encounter with its own medical necessity documentation, not as a repeat test on the original patient.

Why does genetic confirmation matter more now than a few years ago?

Three FDA-approved therapies — tafamidis, acoramidis (approved November 2024), and vutrisiran (expanded to ATTR cardiomyopathy in March 2025) — require a confirmed ATTR diagnosis before a cardiologist will prescribe. Genetic testing that once mainly supported family counseling is now frequently the gating step for active treatment decisions.

What's the most common reason these claims get denied?

Missing or generic documentation of the qualifying clinical criteria — the specific cardiac or neurologic presentation, the ancestry or family-history risk factor, and the counseling attestation — rather than the test itself being non-covered. ICD-10 coding to the specific presenting syndrome, not a generic amyloidosis code, also matters for first-pass approval.

Educational disclaimer: This article summarizes publicly available Medicare coverage documentation as of September 12, 2026, for general informational purposes for laboratory, revenue-cycle, and genetic-counseling professionals. It is not legal, billing, coding, or clinical advice. Coverage policy varies by Medicare Administrative Contractor and can change; laboratories and clinicians should confirm current LCD and billing-article language directly with their MAC and consult qualified coding and compliance staff before submitting claims.

Sources: CMS Medicare Coverage Database, LCD L39935, "MolDX: Molecular Testing for Identification and Management of Hereditary Transthyretin Amyloidosis" (Palmetto GBA, effective August 17, 2025); CMS Medicare Coverage Database, Billing and Coding Article A59849 (revision effective September 25, 2025); CMS Medicare Coverage Database "What's New" report (local coverage), accessed September 2026, showing CGS Administrators Article A59862 revised September 3, 2026; AJMC, "Hereditary ATTR Amyloidosis: Burden of Illness and Diagnostic Challenges"; ARUP Consult, "Familial Transthyretin Amyloidosis (TTR) Sequencing" test fact sheet; FDA approval records for tafamidis (Vyndaqel), acoramidis (Attruby, approved November 2024), and vutrisiran (Amvuttra, ATTR-CM approval March 2025).