ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1191G>C (p.Lys397Asn)

dbSNP: rs1035794713
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000817414 SCV000957971 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 397 of the SDHA protein (p.Lys397Asn). This variant is not present in population databases (gnomAD no frequency). 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: 660259). 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 with a negative predictive value of 95%. 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.
Institute of Human Genetics, Clinical Exome/Genome Diagnostics Group, University Hospital Bonn RCV001843554 SCV002103047 uncertain significance Neurodegeneration with ataxia and late-onset optic atrophy 2021-12-08 criteria provided, single submitter clinical testing PM2
Ambry Genetics RCV002336693 SCV002642747 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-31 criteria provided, single submitter clinical testing The p.K397N variant (also known as c.1191G>C), located in coding exon 9 of the SDHA gene, results from a G to C substitution at nucleotide position 1191. The lysine at codon 397 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly 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.

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