Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000531857 | SCV000623816 | uncertain significance | Hypertrophic cardiomyopathy | 2020-05-29 | 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TPM1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with alanine at codon 30 of the TPM1 protein (p.Lys30Ala). The  lysine residue is weakly  conserved and there is a moderate physicochemical difference between  lysine  and alanine. |