ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1949A>G (p.Asn650Ser)

gnomAD frequency: 0.00001  dbSNP: rs1485747007
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000794100 SCV000933488 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2022-11-04 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 640960). This variant has not been reported in the literature in individuals affected with SDHA-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 650 of the SDHA protein (p.Asn650Ser). 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.
Ambry Genetics RCV002406734 SCV002719343 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-30 criteria provided, single submitter clinical testing The p.N650S variant (also known as c.1949A>G), located in coding exon 15 of the SDHA gene, results from an A to G substitution at nucleotide position 1949. The asparagine at codon 650 is replaced by serine, an amino acid with highly similar properties. This alteration has been observed in at least one individual with a personal and/or family history that is consistent with SDHA-related disease (Ambry internal data). This amino acid position is not well conserved in available vertebrate species. 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.
Fulgent Genetics, Fulgent Genetics RCV002487656 SCV002782088 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy 2021-11-02 criteria provided, single submitter clinical testing

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