ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.455G>A (p.Gly152Glu)

dbSNP: rs1060501386
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001022697 SCV001184464 likely pathogenic Hereditary cancer-predisposing syndrome 2021-02-25 criteria provided, single submitter clinical testing The p.G152E variant (also known as c.455G>A), located in coding exon 6 of the SDHC gene, results from a G to A substitution at nucleotide position 455. The glycine at codon 152 is replaced by glutamic acid, an amino acid with similar properties. This variant has been detected in multiple individuals with a paraganglioma (Ambry internal data). Based on internal structural analysis, the variant disrupts a region of SDHC near key binding sites (Zhou Q et al. Protein Cell, 2011 Jul;2:531-42). This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862227 SCV002108925 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2022-09-07 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHC protein function. ClinVar contains an entry for this variant (Variation ID: 825000). This missense change has been observed in individual(s) with paraganglioma (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 152 of the SDHC protein (p.Gly152Glu).

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