Submissions for variant NM_000257.4(MYH7):c.4828G>C (p.Glu1610Gln)

dbSNP: rs730880810

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000158673	SCV000208608	likely pathogenic	not provided	2012-12-04	criteria provided, single submitter	clinical testing	p.Glu1610Gln (GAG>CAG): c.4828 G>C in exon 34 of the MYH7 gene (NM_000257.2). The Glu1610Gln variant in the MYH7 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Glu1610Gln results in a semi-conservative amino acid substitution of a negatively charged Glutamic acid with a neutral, polar Glutamine at a position that is conserved across species. In silico analysis predicts Glu1610Gln is probably damaging to the protein structure/function. The NHLBI ESP Exome Variant Server reports Glu1610Gln was not observed in approximately 6,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with cardiomyopathy, indicating this region of the protein may be tolerant of change. In summary, while Glu1610Gln is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in DCM panel(s).
Labcorp Genetics (formerly Invitae), Labcorp	RCV001057246	SCV001221729	uncertain significance	Hypertrophic cardiomyopathy	2024-12-08	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 1610 of the MYH7 protein (p.Glu1610Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of dilated cardiomyopathy (PMID: 26406308). ClinVar contains an entry for this variant (Variation ID: 181267). 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV003149964	SCV003838746	uncertain significance	Cardiomyopathy	2021-07-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003298183	SCV003993398	uncertain significance	Cardiovascular phenotype	2024-11-27	criteria provided, single submitter	clinical testing	The p.E1610Q variant (also known as c.4828G>C), located in coding exon 32 of the MYH7 gene, results from a G to C substitution at nucleotide position 4828. The glutamic acid at codon 1610 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Marston S et al. PLoS One, 2015 Sep;10:e0138568). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health	RCV003149964	SCV005430789	uncertain significance	Cardiomyopathy	2024-07-20	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glutamine at codon 1610 of the MYH7 protein. Computational prediction tools indicate that this variant has a deleterious impact on protein structure and function. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in one family affected with dilated cardiomyopathy, and segregated with disease in multiple affected individuals (PMID: 26406308, 29892087). 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.
Fulgent Genetics, Fulgent Genetics	RCV005003504	SCV005629707	uncertain significance	Hypertrophic cardiomyopathy 1; Myopathy, myosin storage, autosomal recessive; Myosin storage myopathy; Dilated cardiomyopathy 1S; MYH7-related skeletal myopathy	2024-05-02	criteria provided, single submitter	clinical testing