ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2005C>T (p.Arg669Ter) (rs111033201)

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
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000844716 SCV000059725 pathogenic Rare genetic deafness 2013-11-22 criteria provided, single submitter clinical testing The p.Arg669X variant in MYO7A has been previously reported in at least 4 indivi duals with Usher syndrome (Bonnet 2011, Roux 2011, LMM-unpublished data). It has also been identified in 0.003% (5/127112) of European chromosomes by gnomAD (ht tp://gnomad.broadinstitute.org), though this frequency in the general population is consistent with a recessive carrier frequency. This nonsense variant leads t o a premature termination codon at position 669, which is predicted to lead to a truncated or absent protein. In summary, this variant meets criteria to be clas sified as pathogenic for autosomal recessive Usher syndrome. ACMG/AMP criteria a pplied: PVS1, PM2, PM3.
Counsyl RCV000036073 SCV000487454 likely pathogenic Usher syndrome type 1 2016-11-02 criteria provided, single submitter clinical testing
Counsyl RCV000409801 SCV000487455 likely pathogenic Deafness, autosomal recessive 2 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000443077 SCV000521011 pathogenic not provided 2017-11-06 criteria provided, single submitter clinical testing The R669X pathogenic variant in the MYO7A gene has been reported previously in the homozygous state or with another MYO7A variant in multiple individuals with Usher syndrome (Bonnet et al., 2011; Roux et al., 2011; Bujakowska et al., 2014; Krawitz et al., 2014). This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R669X variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. We interpret R669X as a pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000443077 SCV000862221 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000763277 SCV000893921 pathogenic Deafness, autosomal dominant 11; Deafness, autosomal recessive 2; Usher syndrome type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000443077 SCV001220993 pathogenic not provided 2019-12-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg669*) in the MYO7A gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs111033201, ExAC 0.007%). This variant has been observed in several individuals affected with Usher syndrome and nonsyndromic sensorineural hearing loss (PMID: 27460420, 25788563, 21569298, 28041643, 21436283, 25333064). ClinVar contains an entry for this variant (Variation ID: 43169). Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236). For these reasons, this variant has been classified as Pathogenic.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000443077 SCV001247934 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504864 SCV000599116 pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research

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.