ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3476G>T (p.Gly1159Val) (rs199897298)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000036110 SCV000059762 likely pathogenic Rare genetic deafness 2016-10-13 criteria provided, single submitter clinical testing The p.Gly1159Val variant in MYO7A has been reported in 9 individuals with hearin g loss (Roux 2011, Schrauwen 2013, LMM data). Four of these individuals were co mpound heterozygous with a second pathogenic or likely pathogenic MYO7A variant, with no indication of retinitis pigmentosa associated with Usher syndrome. Anot her with retinitis pigmentosa had a second variant of uncertain significance in MYO7A. This individual also reportedly has LCHAD, which may explain the retiniti s pigmentosa. This variant has been identified in 12/30732 (0.04%) of European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs199897298); however, this frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conserva tion analysis suggest that this variant may impact the protein, though this info rmation is not predictive enough to determine pathogenicity. In summary, althoug h additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive hearing loss. However, it cannot be determined whether this variant causes type 1 Usher syndrome, atyp ical Usher syndrome, or nonsyndromic hearing loss without additional information .
GeneDx RCV000312187 SCV000329830 pathogenic not provided 2021-07-20 criteria provided, single submitter clinical testing 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: 27535533, 32795431, 30245029, 26486028, 26969326, 27160483, 27068579, 21436283, 23208854)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000312187 SCV000705705 pathogenic not provided 2017-02-09 criteria provided, single submitter clinical testing
Blueprint Genetics RCV001073977 SCV001239543 likely pathogenic Retinal dystrophy 2018-09-04 criteria provided, single submitter clinical testing
Invitae RCV000312187 SCV001419975 uncertain significance not provided 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 1159 of the MYO7A protein (p.Gly1159Val). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs199897298, ExAC 0.04%). This variant has been observed in individual(s) with nonsyndromic hearing loss or an inherited retinal disorder (PMID: 26969326, 27160483, 21436283, 26486028). ClinVar contains an entry for this variant (Variation ID: 43206). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Knight Diagnostic Laboratories, Oregon Health and Sciences University RCV001270103 SCV001448929 likely pathogenic Hearing loss 2019-08-15 criteria provided, single submitter clinical testing
Counsyl RCV000664879 SCV000788903 likely pathogenic Deafness, autosomal recessive 2 2017-01-04 no assertion criteria provided clinical testing
Natera, Inc. RCV001272512 SCV001454584 likely pathogenic Usher syndrome, type 1B 2020-09-16 no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000312187 SCV001951762 likely pathogenic not provided no assertion criteria provided clinical testing

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