ClinVar Miner

Submissions for variant NM_173477.5(USH1G):c.1258C>G (p.Leu420Val) (rs139897506)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000041414 SCV000065109 uncertain significance not specified 2016-07-21 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Leu420Val var iant in USH1G has now been identified in 2 individuals with Usher syndrome and 5 individuals with hearing loss. One of the individuals with Usher syndrome had t wo pathogenic variants in another gene which explained the disease (Glockle 2014 ). A variant affecting the remaining copy of USH1G was not detected in any of th e other individuals (LMM data). This variant has been identified in 0.2% (109/62 876) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://e; dbSNP rs139897506). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathog enic role. Computational prediction tools and conservation analyses do not provi de strong support for or against an impact to the protein. In summary, while the clinical significance of the p.Leu420Val variant is uncertain, these data sugge st that it is more likely to be benign.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724716 SCV000227576 uncertain significance not provided 2015-04-01 criteria provided, single submitter clinical testing
Invitae RCV000724716 SCV001219451 uncertain significance not provided 2019-12-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 420 of the USH1G protein (p.Leu420Val). The leucine residue is highlyconserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs139897506, ExAC 0.2%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals with USH1G-related conditions. ClinVar contains an entry for this variant (Variation ID: 48126). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Clinical Services Laboratory,Illumina RCV001123313 SCV001282137 uncertain significance Usher syndrome, type 1G 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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.