ClinVar Miner

Submissions for variant NM_000371.4(TTR):c.385G>T (p.Ala129Ser)

dbSNP: rs267607159
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770562 SCV000902010 uncertain significance Cardiomyopathy 2015-12-01 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001378795 SCV001576453 pathogenic Amyloidosis, hereditary systemic 1 2024-03-26 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 129 of the TTR protein (p.Ala129Ser). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hereditary transthyretin-mediated amyloidosis (hATTR amyloidosis) (PMID: 9268242; Invitae). This variant is also known as p.Ala109Ser. ClinVar contains an entry for this variant (Variation ID: 626843). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TTR protein function with a positive predictive value of 80%. This variant disrupts the p.Ala129 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in individuals with TTR-related conditions (PMID: 28635949), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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