ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1424G>C (p.Cys475Ser)

dbSNP: rs748567636
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000649405 SCV000771233 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-11-11 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with serine, which is neutral and polar, at codon 475 of the SDHA protein (p.Cys475Ser). This variant is present in population databases (rs748567636, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 539640). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt SDHA protein function with a negative predictive value of 95%. 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.
Ambry Genetics RCV003303064 SCV003996997 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-04 criteria provided, single submitter clinical testing The p.C475S variant (also known as c.1424G>C), located in coding exon 10 of the SDHA gene, results from a G to C substitution at nucleotide position 1424. The cysteine at codon 475 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen RCV003432690 SCV004151958 uncertain significance not provided 2023-02-01 criteria provided, single submitter clinical testing SDHA: PM2

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