ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.790G>A (p.Val264Ile)

gnomAD frequency: 0.00014  dbSNP: rs79875849
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
Illumina Laboratory Services, Illumina RCV000310482 SCV000369506 uncertain significance Usher syndrome type 1C 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000825027 SCV000966224 likely benign not specified 2018-03-09 criteria provided, single submitter clinical testing p.Val264Ile in exon 10 of USH1C: This variant is classified as likely benign due to a lack of conservation across species, including mammals. Of note, >40 mamma ls have a Isoleucine (Ile) at this position despite high nearby amino acid conse rvation. In addition, computational prediction tools do not suggest a high likel ihood of impact to the protein. ACMG/AMP Criteria applied:BP4_Strong.
Invitae RCV001068380 SCV001233490 uncertain significance not provided 2022-11-01 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 264 of the USH1C protein (p.Val264Ile). This variant is present in population databases (rs79875849, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 303809). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Natera, Inc. RCV000310482 SCV001462406 uncertain significance Usher syndrome type 1C 2020-04-11 no assertion criteria provided clinical testing

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.