ClinVar Miner

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

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
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
Integrated Genetics/Laboratory Corporation of America 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 2018-11-01 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 several individuals affected with familial amyloid polyneuropathy (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). Experimental studies have shown that this missense change creates an unstable interaction between transthyretin tetramers (PMID: 17503405). This variant disrupts the p.Ile127 amino acid residue in TTR. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 24480837, 22745357), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000014392 SCV000034641 pathogenic Amyloidogenic transthyretin amyloidosis 1994-05-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.