ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.73G>A (p.Gly25Arg) (rs782252317)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000154329 SCV000203991 pathogenic Rare genetic deafness 2016-06-23 criteria provided, single submitter clinical testing The p.Gly25Arg variant in MYO7A has now been identified in the compound heterozy gous state in six individuals with clinical features of Usher syndrome type I a nd segregated with disease in two affected siblings in one family (Liu 1997, Lev y 1997, Le Quesne Stabej 2012, Gao 2014, Lenarduzzi 2015, LMM data). It has been identified in 2/55510 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Although this variant has been identifie d in the general population, its frequency is low enough to be consistent with t he carrier frequency. In summary, this variant meets our criteria to be classifi ed as pathogenic for autosomal recessive Usher syndrome.
Counsyl RCV000674570 SCV000799928 likely pathogenic Deafness, autosomal recessive 2; Usher syndrome type 1 2018-05-14 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073538 SCV001239085 pathogenic Retinal dystrophy 2019-05-13 criteria provided, single submitter clinical testing
Invitae RCV001224495 SCV001396692 pathogenic not provided 2019-06-27 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 25 of the MYO7A protein (p.Gly25Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs782252317, ExAC 0.004%). This variant has been observed to segregate with clinical features of Usher syndrome in a family (PMID: 25080338) and it has been reported in combination with another MYO7A variant in individuals affected with this condition (PMID: 15660226, 22135276). ClinVar contains an entry for this variant (Variation ID: 177722). This variant has been reported to affect MYO7A protein function (PMID: 18700726). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.

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