ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.781C>T (p.Arg261Cys)

gnomAD frequency: 0.00001  dbSNP: rs143484394
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649447 SCV000771275 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-12-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 261 of the SDHA protein (p.Arg261Cys). This variant is present in population databases (rs143484394, gnomAD 0.004%). 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: 539677). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHA 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.
Ambry Genetics RCV002406450 SCV002669618 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-31 criteria provided, single submitter clinical testing The p.R261C variant (also known as c.781C>T), located in coding exon 7 of the SDHA gene, results from a C to T substitution at nucleotide position 781. The arginine at codon 261 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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