ClinVar Miner

Submissions for variant NM_000256.3(MYBPC3):c.263T>A (p.Val88Asp)

gnomAD frequency: 0.00003  dbSNP: rs730880583
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000158204 SCV000208139 uncertain significance not provided 2018-07-31 criteria provided, single submitter clinical testing This variant is denoted p.Val88Asp (GTC>GAC): c.263 T>A in exon 2 of the MYBPC3 gene (NM_000256.3). The Val88Asp variant in the MYBPC3 gene has not been reported previously as a disease-causing mutation nor as a benign polymorphism, to our knowledge. Val88Asp results in a non-conservative amino acid substitution of a non-polar Valine with a negatively charged Aspartic acid at a residue that is conserved across species. As a result, in silico analysis predicts Val88Asp is probably damaging to the protein structure/function. In addition, the NHLBI ESP Exome Variant Server reports Val88Asp was not observed in approximately 5,000 samples from individuals of European and African American backgrounds, indicating it is not a common benign variant in these populations. However, few mutations have been reported in this region of the MYBPC3 gene. In summary, the clinical significance of the Val88Asp variant in the MYBPC3 gene is currently unknown. The variant is found in HCM panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV001857563 SCV002134630 uncertain significance Hypertrophic cardiomyopathy 2024-10-15 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 88 of the MYBPC3 protein (p.Val88Asp). 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: 180994). 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 RCV002453537 SCV002738969 uncertain significance Cardiovascular phenotype 2024-02-09 criteria provided, single submitter clinical testing The p.V88D variant (also known as c.263T>A), located in coding exon 2 of the MYBPC3 gene, results from a T to A substitution at nucleotide position 263. The valine at codon 88 is replaced by aspartic acid, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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