ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.3010C>G (p.Gln1004Glu)

gnomAD frequency: 0.00001  dbSNP: rs730880762
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158582 SCV000208517 uncertain significance not provided 2018-02-07 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH7 gene. The Q1004E variant has not been published as pathogenic or been reported as benign to our knowledge. It is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The Q1004E variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as thee residues differ in some properties. However, in silico analysis, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Additional evidence is needed to clarify pathogenicity, including significant observation in affected individuals, informative segregation data, and functional evidence.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV001065622 SCV001230589 uncertain significance Hypertrophic cardiomyopathy 2022-11-15 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 181209). This variant has not been reported in the literature in individuals affected with MYH7-related conditions. This variant is present in population databases (rs730880762, gnomAD 0.007%). This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 1004 of the MYH7 protein (p.Gln1004Glu).
Color Diagnostics, LLC DBA Color Health RCV001187172 SCV001353887 uncertain significance Cardiomyopathy 2022-10-20 criteria provided, single submitter clinical testing This missense variant replaces glutamine with glutamic acid at codon 1004 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 cardiovascular disorders in the literature. This variant has been identified in 1/251494 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 RCV002433703 SCV002753332 uncertain significance Cardiovascular phenotype 2019-12-19 criteria provided, single submitter clinical testing The p.Q1004E variant (also known as c.3010C>G), located in coding exon 22 of the MYH7 gene, results from a C to G substitution at nucleotide position 3010. The glutamine at codon 1004 is replaced by glutamic acid, an amino acid with highly similar properties. This amino acid position is highly 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.
Fulgent Genetics, Fulgent Genetics RCV002478479 SCV002783563 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 2022-04-20 criteria provided, single submitter clinical testing

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