Submissions for variant NM_000257.4(MYH7):c.3814G>A (p.Asp1272Asn)

gnomAD frequency: 0.00006  dbSNP: rs730880906

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158860	SCV000208795	uncertain significance	not provided	2024-06-11	criteria provided, single submitter	clinical testing	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; This variant is associated with the following publications: (PMID: 34542152)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000821381	SCV000962136	uncertain significance	Hypertrophic cardiomyopathy	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 1272 of the MYH7 protein (p.Asp1272Asn). This variant is present in population databases (rs730880906, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. ClinVar contains an entry for this variant (Variation ID: 181385). 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 MYH7 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.
Color Diagnostics, LLC DBA Color Health	RCV001180079	SCV001344933	uncertain significance	Cardiomyopathy	2023-09-20	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 1272 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 15/282870 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV002354392	SCV002620216	benign	Cardiovascular phenotype	2024-03-06	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Revvity Omics, Revvity	RCV000158860	SCV003817678	uncertain significance	not provided	2019-08-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV001180079	SCV004817137	uncertain significance	Cardiomyopathy	2024-02-05	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with asparagine at codon 1272 of the MYH7 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 15/282870 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.