ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.5944G>A (p.Gly1982Arg)

gnomAD frequency: 0.00001  dbSNP: rs761469964
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000591647 SCV000706351 pathogenic not provided 2017-02-09 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001074974 SCV001240582 pathogenic Retinal dystrophy 2017-11-05 criteria provided, single submitter clinical testing
Invitae RCV000591647 SCV001589414 pathogenic not provided 2023-12-26 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1982 of the MYO7A protein (p.Gly1982Arg). This variant also falls at the last nucleotide of exon 43, which is part of the consensus splice site for this exon. This variant is present in population databases (rs761469964, gnomAD 0.002%). This missense change has been observed in individuals with autosomal recessive Usher syndrome (PMID: 18181211, 22135276, 25404053). ClinVar contains an entry for this variant (Variation ID: 500416). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects MYO7A function (PMID: 18181211). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20052763). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000591647 SCV002575124 pathogenic not provided 2022-09-20 criteria provided, single submitter clinical testing Non-canonical splice site variant demonstrated to result in loss of function (Le Guedard-Mereuze et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20132242, 23647439, 21436283, 20052763, 18181211, 21031134, 28660889, 31479088, 33576163, 25404053)
Natera, Inc. RCV001829663 SCV002088530 pathogenic Usher syndrome type 1B 2020-07-21 no assertion criteria provided clinical testing

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