Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001305405 | SCV001494740 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2020-08-20 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with phenylalanine at codon 162 of the SDHC protein (p.Ser162Phe). The serine residue is weakly conserved and there is a large physicochemical difference between serine and phenylalanine. 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 SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). 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. |
All of Us Research Program, |
RCV004005028 | SCV004824872 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2023-05-04 | criteria provided, single submitter | clinical testing | This missense variant replaces serine with phenylalanine at codon 162 of the SDHC protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHC-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |