ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.445G>A (p.Ala149Thr)

gnomAD frequency: 0.00002  dbSNP: rs575617625
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000571754 SCV000674965 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-14 criteria provided, single submitter clinical testing The p.A149T variant (also known as c.445G>A), located in coding exon 4 of the SDHA gene, results from a G to A substitution at nucleotide position 445. The alanine at codon 149 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly 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.
Invitae RCV000702947 SCV000831824 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 149 of the SDHA protein (p.Ala149Thr). This variant is present in population databases (rs575617625, gnomAD 0.01%). 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: 486367). 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.
Fulgent Genetics, Fulgent Genetics RCV000764600 SCV000895697 uncertain significance Leigh syndrome; Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5 2018-10-31 criteria provided, single submitter clinical testing

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