Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000035426 | SCV000059074 | uncertain significance | not specified | 2012-06-22 | criteria provided, single submitter | clinical testing | The Ala562Thr variant in MYBPC3 has not been reported in the literature nor prev iously identified by our laboratory. Alanine (Ala) at position 562 is highly con served in evolution, suggesting that a change may impact the protein. Other comp utational analyses (biochemical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) also support an impact to the protein though the accuracy of these tools is unknown. Additional information is needed to fully assess the clinical signif icance of the Ala562Thr variant. |
Invitae | RCV001216382 | SCV001388178 | uncertain significance | Hypertrophic cardiomyopathy | 2020-10-27 | criteria provided, single submitter | clinical testing | 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 28214152) and an individual affected with dilated cardiomyopathy (Invitae). ClinVar contains an entry for this variant (Variation ID: 42559). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 562 of the MYBPC3 protein (p.Ala562Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. |