T60A is a historical name for the TTR variant now commonly written p.Thr80Ala. Both names can refer to the same substitution; the difference comes from whether protein numbering includes the signal peptide. A report may also describe it as NM_000371.4:c.238A>G. Always check the reference sequence and the complete laboratory description.
This variant is associated with hereditary transthyretin amyloidosis. That association is important for clinical assessment and family counselling, but it does not make the future course identical for everyone who carries it.
Why does one variant have two position numbers?
The TTR precursor includes a 20-amino-acid signal peptide. Older literature often numbers the mature protein after that segment has been removed. Thus threonine at precursor position 80 corresponds to position 60 in the mature-protein convention. “Thr” and “T” both denote threonine; “Ala” and “A” denote alanine.
The ClinVar record for NM_000371.4:c.238A>G documents the modern and legacy descriptions. ClinVar is an evidence archive, not a substitute for the laboratory’s clinical interpretation. Check its review status, condition and supporting assertions when using it.
| Description | How to read it |
|---|---|
| T60A / Thr60Ala | Historical mature-protein numbering |
| p.Thr80Ala / T80A | Protein description including the precursor signal peptide |
| NM_000371.4:c.238A>G | DNA-level description on the specified transcript |
What clinical pattern has been reported?
T60A-associated disease can involve both the nervous system and heart. A 2024 observational report from an Irish amyloidosis network described 24 affected patients, with a median age at diagnosis of 65 years. It reported a mixed cardiac and neurological pattern; carpal tunnel syndrome was the initial manifestation in almost half of this selected cohort. Read the original study.
Those observations describe patients who entered that study. They are not a timetable for an unaffected relative, a penetrance estimate for every carrier or a population prevalence calculation. In particular, age at diagnosis is not necessarily the age at which the underlying process began.
What does an inherited T60A result mean?
A confirmed pathogenic TTR finding should lead to discussion of the person’s current clinical status and the family context. The inheritance is generally autosomal dominant: a heterozygous carrier has a 50% chance of passing the variant to each child. The clinical effects can vary. The GeneReviews overview of hereditary TTR amyloidosis discusses inheritance and variable penetrance.
Fictional teaching example. A person receives a family letter naming “T60A,” while their own laboratory report says “p.Thr80Ala.” Before assuming the results disagree, the genetics team checks the transcript, protein numbering and exact DNA change. Once the identity is confirmed, the next questions concern their health and an appropriate follow-up plan.
Does Irish ancestry establish the diagnosis?
No. A founder association can help explain why a variant appears in certain families, but ancestry is not a diagnostic test. Similarly, lacking known Irish ancestry does not invalidate a properly established laboratory result. Use the actual finding and clinical evidence rather than surname, appearance or a remembered family origin.
The study of TTR variants in large-scale sequencing data illustrates another distinction: the frequency of an allele in a dataset is not the proportion of people with symptomatic amyloidosis. A genetic frequency should not be presented as a disease prevalence.
Questions to ask after a result
- Has the laboratory confirmed that this is the same variant documented in the family?
- Is the result classified as pathogenic or likely pathogenic for the relevant condition?
- Which cardiac, neurological or other assessments are appropriate now?
- Who will coordinate monitoring and explain changes over time?
- Which relatives should be offered a genetics discussion, and what report should they bring?
People considering predictive testing may want to discuss its practical and emotional implications before a sample is taken. Family members can make different informed choices. A result should be communicated with an explanation, not sent as an unexplained variant code.
How to search the literature accurately
Search both T60A and Thr80Ala, together with TTR or transthyretin. Record the naming convention in a research spreadsheet so that the same variant is not counted twice. Separate affected case series from studies of unselected carriers, and distinguish a cardiac cohort from one recruited through neuropathy services.
For the broader diagnostic pathway, read our hereditary ATTR guide. For population questions, use the UK prevalence explainer. The variant worksheet and paper-comparison tools can help keep molecular descriptions and study populations distinct.