ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.4117C>T (p.Arg1373Ter)

gnomAD frequency: 0.00001  dbSNP: rs766641715
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666120 SCV000790363 pathogenic Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-03-16 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763282 SCV000893926 pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001038543 SCV001202018 pathogenic not provided 2024-01-16 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg1373*) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is present in population databases (rs766641715, gnomAD 0.009%). This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 16470552, 21436283). ClinVar contains an entry for this variant (Variation ID: 551138). For these reasons, this variant has been classified as Pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001038543 SCV001447894 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
GeneDx RCV001038543 SCV001802076 pathogenic not provided 2022-07-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Published functional studies demonstrate defects in electrophysiology, morphology, and pluripotency in p.(R1373*) cell lines that were resolved to levels close to controls by genetic correction of p.(R1373*) (Tang et al., 2016); This variant is associated with the following publications: (PMID: 21436283, 31589614, 33576163, 27013738, 16470552)
Revvity Omics, Revvity RCV001038543 SCV002017706 pathogenic not provided 2021-03-16 criteria provided, single submitter clinical testing
SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation RCV003389476 SCV003927127 pathogenic Usher syndrome 2022-12-31 criteria provided, single submitter research
Neuberg Centre For Genomic Medicine, NCGM RCV004764795 SCV005374824 uncertain significance Usher syndrome type 1 criteria provided, single submitter clinical testing The observed stop gained c.4117C>T(p.Arg1373Ter) variant in MYO7A gene has been reported previously in compound heterozygous state in multiple individuals affected with Usher syndrome (Roux AF, et al., 2011; Jaijo T, et al., 2006; HURPADE, S., et al.). The c.4117C>T variant has been reported with allele frequency of 0.001% in gnomAD Exomes. This variant has been reported to the ClinVar database as Pathogenic (multiple submissions). Computational evidence (MutationTaster - Disease causing) predicts damaging effect on protein structure and function for this variant. The nucleotide change c.4117C>T in MYO7A is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This sequence change creates a premature translational stop signal (p.Arg1373Ter) in the MYO7A gene. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in MYO7A gene have been previously reported to be disease causing (Weston MD, et al., 1996). For these reasons, this variant has been classified as Pathogenic. The same variant in MYO7A gene has been identified in heterozygous state in sibling [SURAJ SHIVAJI GADEKAR, id: 30607400181]. This variant is absent in paternal cousin [Mrs. SHITAL RAM GIRAM, id: 30607400182].
Natera, Inc. RCV001835074 SCV002088436 pathogenic Usher syndrome type 1B 2020-11-13 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.