ClinVar Miner

Submissions for variant NM_001134363.3(RBM20):c.761C>T (p.Ser254Leu)

gnomAD frequency: 0.00016  dbSNP: rs766868824
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000462628 SCV000552922 benign Dilated cardiomyopathy 1DD 2024-01-25 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002230636 SCV002511608 uncertain significance not specified 2022-04-25 criteria provided, single submitter clinical testing Variant summary: RBM20 c.761C>T (p.Ser254Leu) results in a non-conservative amino acid change in 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 3.2e-05 in 153878 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.761C>T has been reported in the literature in at least one individual without clinical information. This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. Co-occurrences with a pathogenic variant has been reported (TTR c.424G>A, p.Val142Ile), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV002393158 SCV002669666 uncertain significance Cardiovascular phenotype 2023-05-10 criteria provided, single submitter clinical testing The p.S254L variant (also known as c.761C>T), located in coding exon 2 of the RBM20 gene, results from a C to T substitution at nucleotide position 761. The serine at codon 254 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV000462628 SCV002814495 uncertain significance Dilated cardiomyopathy 1DD 2021-08-09 criteria provided, single submitter 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.