ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.292G>C (p.Glu98Gln)

dbSNP: rs868819340
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468949 SCV000546497 uncertain significance Hypertrophic cardiomyopathy 2024-01-29 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 98 of the MYBPC3 protein (p.Glu98Gln). This variant also falls at the last nucleotide of exon 2, which is part of the consensus splice site for this exon. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with hypertrophic cardiomyopathy (PMID: 30297972; Invitae). ClinVar contains an entry for this variant (Variation ID: 407337). 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 tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
GeneDx RCV001549952 SCV001770195 uncertain significance not provided 2018-11-01 criteria provided, single submitter clinical testing Variant was reported in association with HCM, although further details were not provided (Carrier et al, 2007); Not observed in large population cohorts (Lek et al., 2016); At the protein level, in silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; At the mRNA level, variant occurs in the last nucleotide position of exon 2. However, in silico splice algorithms do not predict an effect on splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID 407337; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 30297972, 17536430)

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