ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1195G>A (p.Val399Ile)

gnomAD frequency: 0.00001  dbSNP: rs1162724549
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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, Mass General Brigham Personalized Medicine RCV000825400 SCV000966697 uncertain significance not specified 2018-07-03 criteria provided, single submitter clinical testing The p.Val399Ile variant in MYO7A has not been previously reported in individuals with hearing loss or Usher syndrome. This variant has been identified in 1/871 2 African chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad. broadinstitute.org). Computational prediction tools and conservation analyses su ggest that this variant may not impact the protein, though this information is n ot predictive enough to rule out pathogenicity. In summary, the clinical signifi cance of the p.Val399Ile variant is uncertain. ACMG/AMP Criteria applied: BP4, PM2_Supporting.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811507 SCV001471563 uncertain significance not provided 2019-08-01 criteria provided, single submitter clinical testing The MYO7A c.1195G>A; p.Val399Ile variant, to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the general population with an overall allele frequency of 0.0026% (5/193,980 alleles) in the Genome Aggregation Database. The valine at codon 399 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of this variant is uncertain at this time.
Invitae RCV001811507 SCV004511363 uncertain significance not provided 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 399 of the MYO7A protein (p.Val399Ile). 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: 666883). 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 with a negative predictive value of 95%. 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. RCV001835981 SCV002086571 uncertain significance Usher syndrome type 1B 2020-11-02 no assertion criteria provided clinical testing

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