Submissions for variant NM_002473.6(MYH9):c.2221G>A (p.Val741Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003874218	SCV004680918	uncertain significance	not provided	2023-06-06	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. This variant has not been reported in the literature in individuals affected with MYH9-related conditions. This variant is present in population databases (rs140032888, gnomAD 0.008%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 741 of the MYH9 protein (p.Val741Met).
PreventionGenetics, part of Exact Sciences	RCV004733656	SCV005363270	uncertain significance	MYH9-related disorder	2024-07-10	no assertion criteria provided	clinical testing	The MYH9 c.2221G>A variant is predicted to result in the amino acid substitution p.Val741Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.