ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.3661C>G (p.Leu1221Val)

gnomAD frequency: 0.00001  dbSNP: rs1351250957
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000685678 SCV000813168 uncertain significance Hypertrophic cardiomyopathy 2024-09-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1221 of the MYBPC3 protein (p.Leu1221Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MYBPC3-related conditions. ClinVar contains an entry for this variant (Variation ID: 565980). 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.
Ambry Genetics RCV003372801 SCV004096180 uncertain significance Cardiovascular phenotype 2023-06-22 criteria provided, single submitter clinical testing The p.L1221V variant (also known as c.3661C>G), located in coding exon 33 of the MYBPC3 gene, results from a C to G substitution at nucleotide position 3661. The leucine at codon 1221 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV005231262 SCV005875107 uncertain significance not provided 2024-08-21 criteria provided, single submitter clinical testing De novo variant with confirmed parentage in a patient referred for genetic testing at GeneDx; however, the reported clinical features are only partially consistent with the features typically observed in individuals with pathogenic variants in this gene; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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