ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5824G>T (p.Gly1942Ter)

gnomAD frequency: 0.00002  dbSNP: rs111033192
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Total submissions: 12
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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 RCV000036205 SCV000059857 pathogenic Rare genetic deafness 2009-10-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV004528179 SCV000374474 likely pathogenic MYO7A-related disorder 2017-04-27 criteria provided, single submitter clinical testing The MYO7A c.5824G>T (p.Gly1942Ter) variant is a stop-gained variant that is predicted to result in a premature termination of the protein. The p.Gly1942Ter variant has been reported in three studies in which it is found in a total of seven patients including in five in a compound heterozygous state, in one in heterozygous state, and in one allele in a study of 100 Danish patients where zygosity was not specified (Jacobson et al. 2011; Le Quesne Stabej et al. 2011; Dad et al. 2016). The p.Gly1942Ter variant was absent from 486 controls but is reported at a frequency of 0.00004 in the European (non-Finnish) population of the Exome Aggregation Consortium. This frequency is based on two alleles in a region of low sequence coverage. Based on the evidence, the p.Gly1942Ter variant is classified as likely pathogenic for MYO7A-related disorders, although notably has only been described in patients with Usher syndrome and appears to be inherited in an autosomal recessive manner. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Baylor Genetics RCV000665920 SCV001163703 pathogenic Usher syndrome type 1 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001204875 SCV001376103 pathogenic not provided 2024-02-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gly1942*) 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 (rs111033192, gnomAD 0.003%). This premature translational stop signal has been observed in individuals with Usher syndrome (PMID: 21873662, 22135276). ClinVar contains an entry for this variant (Variation ID: 43300). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001204875 SCV002567675 pathogenic not provided 2022-01-22 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: 21873662, 27957503, 31980526, 24199935)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg RCV004814950 SCV005071392 pathogenic Retinal dystrophy 2022-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005007948 SCV005629481 pathogenic Autosomal dominant nonsyndromic hearing loss 11; Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2024-05-31 criteria provided, single submitter clinical testing
Counsyl RCV000665920 SCV000790126 pathogenic Usher syndrome type 1 2017-06-05 no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV001204875 SCV001920344 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001204875 SCV001958001 pathogenic not provided no assertion criteria provided clinical testing
Natera, Inc. RCV001831641 SCV002088524 pathogenic Usher syndrome type 1B 2020-08-11 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004528179 SCV005357732 pathogenic MYO7A-related disorder 2024-09-19 no assertion criteria provided clinical testing The MYO7A c.5824G>T variant is predicted to result in premature protein termination (p.Gly1942*). This variant has been reported along with a second variant allele in MYO7A in individuals with Usher syndrome or MYO7A-related features (Jacobson et al. 2011. PubMed ID: 21873662; Table S1, Lin et al. 2024. PubMed ID: 38219857; Table S1, Mansard et al. 2021. PubMed ID: 34948090). This variant is reported in 0.0027% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in MYO7A are expected to be pathogenic. This variant is interpreted as pathogenic.

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