ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1432G>C (p.Gly478Arg)

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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 RCV003311072 SCV004007442 uncertain significance Hereditary cancer-predisposing syndrome 2023-04-24 criteria provided, single submitter clinical testing The p.G478R variant (also known as c.1432G>C), located in coding exon 10 of the SDHA gene, results from a G to C substitution at nucleotide position 1432. The amino acid change results in glycine to arginine at codon 478, an amino acid with 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV003777241 SCV004574730 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-01-27 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is present in population databases (rs759041443, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 478 of the SDHA protein (p.Gly478Arg). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon.

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