ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs111033201
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham 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in MYO7A has been previously reported in at least 4 indivi duals with Usher syndrome (Bonnet 2011, Roux 2011, LMM-unpublished data).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 Autosomal recessive nonsyndromic hearing loss 2 2016-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000443077 SCV000521011 pathogenic not provided 2020-12-02 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; This variant is associated with the following publications: (PMID: 32581362, 31266775, 31479088, 29892088, 27460420, 25333064, 25468891, 21436283, 21569298, 21873662, 9718356, 25525159)
Eurofins Ntd Llc (ga) RCV000443077 SCV000862221 pathogenic not provided 2018-06-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763277 SCV000893921 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 RCV000443077 SCV001220993 pathogenic not provided 2024-01-12 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. Loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is present in population databases (rs111033201, gnomAD 0.005%). This premature translational stop signal has been observed in individual(s) with Usher syndrome and nonsyndromic sensorineural hearing loss (PMID: 21436283, 21569298, 25333064, 25788563, 27460420, 28041643). ClinVar contains an entry for this variant (Variation ID: 43169). For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000443077 SCV001247934 pathogenic not provided 2019-08-01 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV004528175 SCV004112839 pathogenic MYO7A-related disorder 2023-05-01 criteria provided, single submitter clinical testing The MYO7A c.2005C>T variant is predicted to result in premature protein termination (p.Arg669*). This variant has been reported in compound heterozygous and homozygous state in multiple individuals with Usher syndrome type 1B (see for example - Roux et al. 2011. PubMed ID: 21436283; Table S1 - Bonnet et al. 2016. PubMed ID: 27460420; Table S2 - Carss et al. 2017. PubMed ID: 28041643; Table S1 - Khateb et al. 2019. PubMed ID: 31479088). This variant is reported in 0.0039% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-76885871-C-T). Nonsense variants in MYO7A are expected to be pathogenic. This variant is interpreted as pathogenic.
NIHR Bioresource Rare Diseases, University of Cambridge RCV000504864 SCV000599116 pathogenic Usher syndrome 2015-01-01 no assertion criteria provided research
Natera, Inc. RCV001272498 SCV001454570 pathogenic Usher syndrome type 1B 2020-09-16 no assertion criteria provided clinical testing

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