ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.2512G>C (p.Glu838Gln)

gnomAD frequency: 0.00001  dbSNP: rs397515969
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156245 SCV000205961 uncertain significance not specified 2013-12-11 criteria provided, single submitter clinical testing The Glu838Gln variant in MYBPC3 has not been previously reported in individuals with cardiomyopathy or large European American and African American cohorts. Co mputational analyses (biochemical amino acid properties, conservation, AlignGVGD , PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical sig nificance of the Glu838Gln variant.
Invitae RCV001351680 SCV001546173 uncertain significance Hypertrophic cardiomyopathy 2023-12-21 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 838 of the MYBPC3 protein (p.Glu838Gln). This variant is present in population databases (rs397515969, gnomAD 0.004%). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 32826072). ClinVar contains an entry for this variant (Variation ID: 179456). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Fulgent Genetics, Fulgent Genetics RCV002484948 SCV002779047 uncertain significance Hypertrophic cardiomyopathy 4; Left ventricular noncompaction 10 2021-09-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV003162637 SCV003911377 uncertain significance Cardiovascular phenotype 2023-02-08 criteria provided, single submitter clinical testing The p.E838Q variant (also known as c.2512G>C), located in coding exon 25 of the MYBPC3 gene, results from a G to C substitution at nucleotide position 2512. The glutamic acid at codon 838 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort (Peña-Peña ML et al. Med Clin (Barc), 2021 May;156:485-495). 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.

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