ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1133G>A (p.Arg378His)

gnomAD frequency: 0.00001  dbSNP: rs397516282
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000036040 SCV000059692 uncertain significance not specified 2012-06-26 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Arg378His varia nt in MYO7A has not been reported in the literature nor previously identified by our laboratory. Computational analyses (biochemical amino acid properties, cons ervation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Arg378His variant may not impact the protein, though this information is not predictive enough to rul e out pathogenicity. In summary, the clinical significance of this variant canno t be determined with certainty.
Counsyl RCV000668099 SCV000792648 uncertain significance Autosomal recessive nonsyndromic hearing loss 2; Usher syndrome type 1 2017-07-05 criteria provided, single submitter clinical testing
GeneDx RCV001762113 SCV002000882 uncertain significance not provided 2020-03-13 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV001762113 SCV002207032 uncertain significance not provided 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 378 of the MYO7A protein (p.Arg378His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 43136). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYO7A protein function. 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.
Natera, Inc. RCV001831625 SCV002086568 uncertain significance Usher syndrome type 1B 2020-03-20 no assertion criteria provided clinical testing

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