ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3305T>A (p.Val1102Glu)

dbSNP: rs730880590
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158225 SCV000208160 likely pathogenic not provided 2014-06-12 criteria provided, single submitter clinical testing This variant is denoted p.Val1102Glu (GTG>GAG): c.3305 T>A in exon 30 of the MYBPC3 gene (NM_000256.3). The V1102E variant that is likely pathogenic was identified in the MYBPC3 gene. It has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The V1102E variant was not observed in approximately 6,200 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1102E variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. Furthermore, missense mutations in nearby residues (T1109I, E1111G) have been reported in association with HCM, supporting the functional importance of this region of the protein.Therefore, this variant is a strong candidate for a pathogenic mutation, however the possibility that it is a benign variant cannot be excluded. The variant is found in HCM panel(s).
Invitae RCV003586151 SCV004294782 uncertain significance Hypertrophic cardiomyopathy 2022-11-24 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 181005). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This missense change has been observed in individual(s) with hypertrophic cardiomyopathy (PMID: 29121657). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 1102 of the MYBPC3 protein (p.Val1102Glu).

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