Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV003162251 | SCV003904897 | likely pathogenic | Cardiovascular phenotype | 2023-01-30 | criteria provided, single submitter | clinical testing | The p.L131M variant (also known as c.391C>A), located in coding exon 4 of the TTR gene, results from a C to A substitution at nucleotide position 391. The leucine at codon 131 is replaced by methionine, an amino acid with highly similar properties. This alteration, which is also reported as p.L111M, has been detected in several individuals with transthyretin (TTR) amyloidosis and related cardiomyopathy and TTR amyloidosis cohorts (Nordlie M et al. Scand J Immunol, 1988 Jan;27:119-22; Altland K et al. Electrophoresis, 2007 Jun;28:2053-64; Nelson LM et al. Clin Transplant, 2013 Dec;27:203-9; Suhr OB et al. Transplantation, 2016 Feb;100:373-81; Damy T et al. Eur Heart J, 2019 Apr;43:391-400; Caponetti AG et al. JACC Heart Fail, 2021 Oct;9:736-746; Barroso FA et al. Amyloid, 2022 Sep;29:175-183; Dispenzieri A et al. Orphanet J Rare Dis, 2022 Jun;17:236). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| OMIM | RCV000014366 | SCV000034615 | pathogenic | Amyloidosis, hereditary systemic 1 | 1993-10-01 | no assertion criteria provided | literature only |