ClinVar Miner

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

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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 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 likely pathogenic not provided 2017-12-19 criteria provided, single submitter clinical testing The G1159V variant in the MYO7A gene has been reported previously in association with hearing loss in two unrelated affected individuals who were also heterozygous for a second MYO7A variant (Roux et al., 2011; Schrauwen et al., 2013). The G1159V variant is observed in 12/30732 (0.04%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The G1159V is reported as likely pathogenic in ClinVar by a different clinical laboratory, but additional evidence is not available regarding this submission (ClinVar SCV000059762.4; Landrum et al., 2016). The G1159V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G1159V as likely pathogenic variant.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000312187 SCV000705705 pathogenic not provided 2017-02-09 criteria provided, single submitter clinical testing
Counsyl RCV000664879 SCV000788903 likely pathogenic Deafness, autosomal recessive 2 2017-01-04 no assertion criteria provided clinical testing

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