ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.970G>A (p.Glu324Lys)

gnomAD frequency: 0.00004  dbSNP: rs147014102
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000649457 SCV000771285 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-30 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 324 of the SDHA protein (p.Glu324Lys). This variant is present in population databases (rs147014102, gnomAD 0.05%). 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: 539687). 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.
Counsyl RCV000662695 SCV000785426 uncertain significance Paragangliomas 5 2017-08-03 criteria provided, single submitter clinical testing
Ambry Genetics RCV002369740 SCV002690607 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-25 criteria provided, single submitter clinical testing The p.E324K variant (also known as c.970G>A), located in coding exon 8 of the SDHA gene, results from a G to A substitution at nucleotide position 970. The glutamic acid at codon 324 is replaced by lysine, 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 deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002493038 SCV002790319 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy 2021-08-24 criteria provided, single submitter clinical testing
Myriad Genetics, Inc. RCV000662695 SCV004018577 uncertain significance Paragangliomas 5 2023-04-20 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV003472049 SCV004202396 uncertain significance Dilated cardiomyopathy 1GG 2023-10-09 criteria provided, single submitter clinical testing

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