Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001225763 | SCV001398053 | uncertain significance | Left ventricular noncompaction 8 | 2019-09-12 | criteria provided, single submitter | clinical testing | 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. 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. This variant has not been reported in the literature in individuals with PRDM16-related conditions. This variant is present in population databases (rs768208960, ExAC no frequency). This sequence change replaces methionine with leucine at codon 788 of the PRDM16 protein (p.Met788Leu). The methionine residue is weakly conserved and there is a small physicochemical difference between methionine and leucine. |
Loeys Lab, |
RCV001375650 | SCV001572578 | uncertain significance | Primary dilated cardiomyopathy | 2021-02-26 | criteria provided, single submitter | clinical testing | This sequence change results in a missense variant in the PRDM16 gene (p.(Met788Leu)). This variant is present in population databases with a prevalence of 1/243010 in GnomAD). The variant has not been described before. The variant affects a weakly conserved nucleotide and weakly conserved amino acid. No functional data are available. Prediction programs predict a benign effect (Align GVGD:C0,polymorphism; Polyphen-2-HumDiv: benign; Polyphen-2-HumVar: benign; SIFT: tolerated; Mutation Taster: polymorphism) (BP4). The variant was identified in a patient with DCM. No data on segregation are available. In conclusion this variant was classified as a variant of unknown significance according to ACMG-guidelines (insufficient data, criteria for other classification are not met: BP4). |