ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.2323C>T (p.Gln775Ter)

gnomAD frequency: 0.00001  dbSNP: rs201892914
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410053 SCV000487484 likely pathogenic Usher syndrome type 1 2016-11-10 criteria provided, single submitter clinical testing
Counsyl RCV000411572 SCV000487485 likely pathogenic Autosomal recessive nonsyndromic hearing loss 2 2016-11-10 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000844718 SCV000710855 pathogenic Rare genetic deafness 2016-07-07 criteria provided, single submitter clinical testing The p.Gln775X variant in MYO7A has been reported in the compound heterozygous st ate in one individual with hearing loss who had a likely diagnosis of Usher synd rome (Sloan-Heggen 2016). It has been identified in 1/5994 African chromosomes a nd 2/43186 European chromosome by the Exome Aggregation Consortium (ExAC, http:/ /exac.broadinstitute.org; dbSNP rs201892914); This low frequency in the general population is consistent with the carrier frequency for hearing loss or Usher sy ndrome. This nonsense variant leads to a premature termination codon at position 775, which is predicted to lead to a truncated or absent protein. In summary, t his variant meets our criteria to be classified as pathogenic for Usher syndrome in an autosomal recessive manner.
Labcorp Genetics (formerly Invitae), Labcorp RCV001383210 SCV001582290 pathogenic not provided 2024-01-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln775*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal recessive Usher syndrome (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 371700). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001383210 SCV003923828 pathogenic not provided 2023-05-04 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; Not observed at a significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16963483, 26969326)
Natera, Inc. RCV001828377 SCV002086611 pathogenic Usher syndrome type 1B 2021-02-02 no assertion criteria provided clinical testing

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