ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5804T>C (p.Leu1935Pro) (rs397516323)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Hearing Loss Variant Curation Expert Panel RCV001252670 SCV001428429 likely pathogenic Usher syndrome 2020-06-24 reviewed by expert panel curation The c.5804T>C (p.Leu1935Pro) variant in MYO7A is present in in 0.00236% (3/127394) of European (non-Finnish) chromosomes in gnomAD v2.1.1, which is a low enough frequency to apply PM2 based on the thresholds defined by the ClinGen Hearing Loss Expert Panel for autosomal recessive hearing loss (PM2). The variant has been detected in 1 patient with hearing loss in trans with the pathogenic c.1200+1G>A variant (PM3; Partners LMM internal data, SCV000059855.6). At least one patient with this variant displayed features of hearing loss and retinitis pigmentosa, features highly specific for Usher syndrome (PP4; Blueprint Genetics internal data, SCV001239772.1). The REVEL computation prediction tool produced a score of 0.961, which is above the threshold necessary to apply PP3. In summary, this variant meets criteria to be classified as likely pathogenic for autosomal recessive Usher syndrome based on the ACMG/AMP criteria applied as specified by the Hearing Loss Expert Panel (PM2, PM3, PP3, PP4).
Counsyl RCV000675068 SCV000800545 uncertain significance Deafness, autosomal recessive 2; Usher syndrome type 1 2017-06-02 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074201 SCV001239772 likely pathogenic Retinal dystrophy 2019-03-15 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036203 SCV000059855 likely pathogenic Rare genetic deafness 2010-08-16 no assertion criteria provided clinical testing The Leu1935Pro variant in MYO7A has not been reported in the literature. This re sidue is conserved across species and computational analyses (PolyPhen, SIFT) su ggest that the Leu1935Pro variant may impact the protein. This variant was detec ted in a patient in combination with a reported pathogenic variant increasing th e likelihood that the Leu1935Pro variant is pathogenic. In summary, this variant is likely to be pathogenic.

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