Submissions for variant NM_002473.6(MYH9):c.4975G>A (p.Ala1659Thr)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002573886	SCV002931171	uncertain significance	not provided	2023-08-14	criteria provided, single submitter	clinical testing	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. 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 MYH9 protein function. ClinVar contains an entry for this variant (Variation ID: 1898329). This variant has not been reported in the literature in individuals affected with MYH9-related conditions. 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 sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1659 of the MYH9 protein (p.Ala1659Thr).
PreventionGenetics, part of Exact Sciences	RCV004529151	SCV004109703	uncertain significance	MYH9-related disorder	2023-06-01	criteria provided, single submitter	clinical testing	The MYH9 c.4975G>A variant is predicted to result in the amino acid substitution p.Ala1659Thr. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.