Submissions for variant NM_000257.4(MYH7):c.4756G>A (p.Ala1586Thr)

dbSNP: rs1595073523

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817363	SCV000957917	uncertain significance	Hypertrophic cardiomyopathy	2022-06-23	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 1586 of the MYH7 protein (p.Ala1586Thr). This variant is not present in population databases (gnomAD no frequency). 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: 660218). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	RCV000845472	SCV000987563	uncertain significance	Conduction disorder of the heart		criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV002487807	SCV002787101	uncertain significance	Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Congenital myopathy with fiber type disproportion; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy	2021-08-11	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV003532279	SCV004359525	uncertain significance	Cardiomyopathy	2023-04-23	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 1586 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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.
All of Us Research Program, National Institutes of Health	RCV003532279	SCV004832437	uncertain significance	Cardiomyopathy	2023-11-30	criteria provided, single submitter	clinical testing	This missense variant replaces alanine with threonine at codon 1586 of the MYH7 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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	RCV004639380	SCV005143076	uncertain significance	Cardiovascular phenotype	2024-04-12	criteria provided, single submitter	clinical testing	The p.A1586T variant (also known as c.4756G>A), located in coding exon 32 of the MYH7 gene, results from a G to A substitution at nucleotide position 4756. The alanine at codon 1586 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.