ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1951G>C (p.Glu651Gln)

dbSNP: rs375396913
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000662705 SCV000785452 uncertain significance Paragangliomas 5 2017-08-12 criteria provided, single submitter clinical testing
Invitae RCV000793459 SCV000932811 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 651 of the SDHA protein (p.Glu651Gln). This variant is present in population databases (rs375396913, gnomAD 0.006%). 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: 548773). 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.
Ambry Genetics RCV002422447 SCV002719375 uncertain significance Hereditary cancer-predisposing syndrome 2024-03-24 criteria provided, single submitter clinical testing The p.E651Q variant (also known as c.1951G>C), located in coding exon 15 of the SDHA gene, results from a G to C substitution at nucleotide position 1951. The glutamic acid at codon 651 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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