Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000641786 | SCV000763435 | uncertain significance | Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 | 2021-08-12 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine with leucine at codon 65 of the DSP protein (p.His65Leu). The histidine residue is moderately conserved and there is a moderate physicochemical difference between histidine and leucine. This variant is present in population databases (rs771190708, ExAC 0.002%). This missense change has been observed in individual(s) with clinical features of DSP-related conditions (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The leucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |