ClinVar Miner

Submissions for variant NM_000257.4(MYH7):c.4042G>A (p.Glu1348Lys)

gnomAD frequency: 0.00001  dbSNP: rs1275262402
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000628908 SCV000749816 uncertain significance Hypertrophic cardiomyopathy 2023-10-14 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1348 of the MYH7 protein (p.Glu1348Lys). This variant is present in population databases (no rsID available, gnomAD 0.01%). This missense change has been observed in individual(s) with hypertrophic cardiomyopathy, left ventricular noncompaction cardiomyopathy (PMID: 25132132, 34036930, 36264615). ClinVar contains an entry for this variant (Variation ID: 524974). 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 RCV001189994 SCV001357403 uncertain significance Cardiomyopathy 2019-06-08 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 1348 of the MYH7 protein. Computational prediction tools and conservation analyses suggest that this variant may have deleterious impact on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant. This variant has been reported in an individual affected with hypertrophic cardiomyopathy (PMID: 25132132). This variant has also been identified in 1/31400 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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.
GeneDx RCV001551781 SCV001772358 uncertain significance not provided 2019-11-21 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 29540472, 25132132)
Fulgent Genetics, Fulgent Genetics RCV002492934 SCV002775802 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 2021-10-19 criteria provided, single submitter clinical testing

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