Submissions for variant NM_000257.4(MYH7):c.4868A>G (p.Asn1623Ser)

gnomAD frequency: 0.00003  dbSNP: rs1306407579

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000629007	SCV000749917	uncertain significance	Hypertrophic cardiomyopathy	2024-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 1623 of the MYH7 protein (p.Asn1623Ser). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 525032). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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	RCV001179128	SCV001343735	uncertain significance	Cardiomyopathy	2023-07-06	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 1623 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 MYH7-related disorders in the literature. This variant has been identified in 4/282880 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.
All of Us Research Program, National Institutes of Health	RCV001179128	SCV004831357	uncertain significance	Cardiomyopathy	2023-12-13	criteria provided, single submitter	clinical testing	This missense variant replaces asparagine with serine at codon 1623 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 MYH7-related disorders in the literature. This variant has been identified in 4/282880 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001796145	SCV002034972	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001796145	SCV002037284	uncertain significance	not provided		no assertion criteria provided	clinical testing