ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1765C>G (p.Arg589Gly)

dbSNP: rs387906780
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001234597 SCV001407251 likely pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-08-16 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 960976). This missense change has been observed in individual(s) with gastrointestinal stromal tumor (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 589 of the SDHA protein (p.Arg589Gly). 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 SDHA protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg589 amino acid residue in SDHA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20484225, 22955521, 23043141, 25405498, 28546994). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects SDHA function (PMID: 28724664).

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