ClinVar Miner

Submissions for variant NM_000371.3(TTR):c.379A>G (p.Ile127Val) (rs121918089)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000506089 SCV000605507 likely pathogenic not specified 2017-03-01 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000014392 SCV000696632 pathogenic Amyloidogenic transthyretin amyloidosis 2016-02-26 criteria provided, single submitter clinical testing Variant summary: The TTR c.379A>G variant affects a conserved nucleotide, resulting in amino acid change from Ile to Val. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). However, functional studies indicate that TTRI107V dimers and tetramers decreased stability compared to controls. This variant is not found in 121416 control chromosomes, but has been cited in numerous ATTR patients from various ethnicities. Taken together, this is a disease variant and was classified as pathogenic.
Invitae RCV000014392 SCV000769146 pathogenic Amyloidogenic transthyretin amyloidosis 2020-08-27 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 127 of the TTR protein (p.Ile127Val). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with amyloidosis (PMID: 9748014, 20209591, 26537620, 27025994, 27066555, 7914929, 8081397, 24101130). This variant is also known as p.Ile107Val in the literature. ClinVar contains an entry for this variant (Variation ID: 13450). This variant has been reported to affect TTR protein function (PMID: 17503405). The p.Ile127 amino acid residue in TTR has been determined to be clinically significant (PMID: 24480837, 22745357). This suggests that variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
Mendelics RCV000014392 SCV001140874 pathogenic Amyloidogenic transthyretin amyloidosis 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV001090344 SCV001245843 pathogenic not provided 2019-03-01 criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001090344 SCV001446722 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV001090344 SCV001476395 pathogenic not provided 2019-12-16 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality. Found in multiple individuals with expected phenotype for this gene. Assessment of experimental evidence suggests this variant results in abnormal protein function.
OMIM RCV000014392 SCV000034641 pathogenic Amyloidogenic transthyretin amyloidosis 1994-05-01 no assertion criteria provided literature only

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