ClinVar Miner

Submissions for variant NM_000260.4(MYO7A):c.1606G>A (p.Ala536Thr)

gnomAD frequency: 0.00003  dbSNP: rs201046979
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Total submissions: 3
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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 RCV000036058 SCV000059710 likely benign not specified 2011-11-01 criteria provided, single submitter clinical testing Ala536Thr in exon 14 of MYO7A: This variant is not expected to have clinical sig nificance because it has been identified by our laboratory in one individual who also carried two pathogenic MYO7A variants. In addition, computational analyses (PolyPhen2, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein primarily based upon a lack of conservation across species including mam mals. Of note, opossum, chicken, frog and zebrafish have a threonine (Thr) at th is position despite high nearby amino acid conservation.
Invitae RCV001049904 SCV001213978 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 536 of the MYO7A protein (p.Ala536Thr). This variant is present in population databases (rs201046979, gnomAD 0.03%). 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: 43154). 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.
GeneDx RCV001049904 SCV003805175 uncertain significance not provided 2022-08-18 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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