ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1423T>C (p.Cys475Arg)

gnomAD frequency: 0.00002  dbSNP: rs781747137
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000234575 SCV000288109 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2022-10-16 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 475 of the SDHA protein (p.Cys475Arg). This variant is present in population databases (rs781747137, gnomAD 0.01%). 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: 239646). 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 not expected to disrupt 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.
Counsyl RCV000663132 SCV000786271 uncertain significance Paragangliomas 5 2018-04-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002392698 SCV002702704 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-18 criteria provided, single submitter clinical testing The p.C475R variant (also known as c.1423T>C), located in coding exon 10 of the SDHA gene, results from a T to C substitution at nucleotide position 1423. The cysteine at codon 475 is replaced by arginine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Myriad Genetics, Inc. RCV000663132 SCV004045423 uncertain significance Paragangliomas 5 2023-04-21 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003475068 SCV004200634 uncertain significance Dilated cardiomyopathy 1GG 2023-06-13 criteria provided, single submitter clinical testing

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