ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1928C>G (p.Pro643Arg)

gnomAD frequency: 0.00001  dbSNP: rs1060503717
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000459590 SCV000553890 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2021-07-17 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a SDHA-related disease. In summary, this variant is a novel missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance. 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 tolerated, but these predictions have not been confirmed by published functional studies. This sequence change replaces proline with arginine at codon 643 of the SDHA protein (p.Pro643Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine.
Fulgent Genetics, Fulgent Genetics RCV002475894 SCV002778009 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy 2021-10-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV003168871 SCV003901707 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-02 criteria provided, single submitter clinical testing The p.P643R variant (also known as c.1928C>G), located in coding exon 15 of the SDHA gene, results from a C to G substitution at nucleotide position 1928. The proline at codon 643 is replaced by arginine, 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.

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