ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.3836C>T (p.Thr1279Met)

gnomAD frequency: 0.00002  dbSNP: rs766245260
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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 RCV000608638 SCV000731768 uncertain significance not specified 2017-07-27 criteria provided, single submitter clinical testing The p.Thr1279Met variant in MYO7A has not been previously reported in individual s with hearing loss or Usher syndrome, but has been identified 1/96932 European chromosomes by the Genome Aggregation Consortium (gnomAD, http://gnomad.broadins titute.org; dbSNP rs766245260). Although this variant has been seen in the gener al population, its frequency is not high enough to rule out a pathogenic role. C omputational prediction tools and conservation analyses suggest that this varian t may impact the protein, though this information is not predictive enough to de termine pathogenicity. In summary, the clinical significance of the p.Thr1279Met variant is uncertain.
Ambry Genetics RCV002528788 SCV003674722 uncertain significance Inborn genetic diseases 2022-12-16 criteria provided, single submitter clinical testing The c.3836C>T (p.T1279M) alteration is located in exon 30 (coding exon 29) of the MYO7A gene. This alteration results from a C to T substitution at nucleotide position 3836, causing the threonine (T) at amino acid position 1279 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003736858 SCV004551539 uncertain significance not provided 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1279 of the MYO7A protein (p.Thr1279Met). 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: 517473). 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 expected to disrupt MYO7A protein function with a positive predictive value of 80%. 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.
GeneDx RCV003736858 SCV005370052 uncertain significance not provided 2023-06-01 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001834958 SCV002086687 uncertain significance Usher syndrome type 1B 2021-10-15 no assertion criteria provided clinical testing

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