Submissions for variant NM_020884.7(MYH7B):c.4279C>T (p.Arg1427Trp)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
PreventionGenetics, part of Exact Sciences	RCV003392856	SCV004119022	uncertain significance	MYH7B-related disorder	2023-07-07	criteria provided, single submitter	clinical testing	The MYH7B c.4405C>T variant is predicted to result in the amino acid substitution p.Arg1469Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.014% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/20-33586947-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003732571	SCV004530106	uncertain significance	not provided	2023-08-17	criteria provided, single submitter	clinical testing	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 MYH7B 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. This variant has not been reported in the literature in individuals affected with MYH7B-related conditions. This variant is present in population databases (rs376694362, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1469 of the MYH7B protein (p.Arg1469Trp).