ClinVar Miner

Submissions for variant NM_021830.5(TWNK):c.1802G>A (p.Arg601Gln)

gnomAD frequency: 0.00003  dbSNP: rs141315771
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV001663645 SCV001880639 uncertain significance not provided 2020-12-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002300566 SCV002599054 uncertain significance not specified 2022-08-22 criteria provided, single submitter clinical testing Variant summary: C10orf2 (also known as TWNK) c.1802G>A/p.Arg601Gln results in a conservative amino acid change located in the DNA helicase, DnaB-like, C-terminal domain (IPR007694) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 282894 control chromosomes (gnomAD). c.1802G>A has been reported as a biallelic genotype in the literature in two sisters affected with Perrault syndrome (Oldak_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV001663645 SCV004127229 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing TWNK: PM2, BP4
Labcorp Genetics (formerly Invitae), Labcorp RCV001663645 SCV005835925 pathogenic not provided 2024-09-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 601 of the TWNK protein (p.Arg601Gln). This variant is present in population databases (rs141315771, gnomAD 0.006%). This missense change has been observed in individual(s) with autosomal recessive Perrault syndrome (PMID: 28178980). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1256303). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TWNK protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV002539653 SCV003525966 not provided Perrault syndrome no assertion 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.