ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1462G>A (p.Ala488Thr)

gnomAD frequency: 0.00005  dbSNP: rs369100772
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000468600 SCV000553917 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2025-01-16 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 488 of the SDHA protein (p.Ala488Thr). This variant is present in population databases (rs369100772, gnomAD 0.008%). 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: 412393). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV000562914 SCV000674975 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-26 criteria provided, single submitter clinical testing The p.A488T variant (also known as c.1462G>A), located in coding exon 11 of the SDHA gene, results from a G to A substitution at nucleotide position 1462. The alanine at codon 488 is replaced by threonine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000714730 SCV000845458 uncertain significance Leigh syndrome 2018-08-07 criteria provided, single submitter clinical testing
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000714731 SCV000845459 uncertain significance Mitochondrial complex II deficiency, nuclear type 1 2018-08-07 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002481484 SCV002786092 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Dilated cardiomyopathy 1GG; Paragangliomas 5; Neurodegeneration with ataxia and late-onset optic atrophy 2024-06-18 criteria provided, single submitter clinical testing
Baylor Genetics RCV003476133 SCV004200646 uncertain significance Dilated cardiomyopathy 1GG 2023-05-18 criteria provided, single submitter clinical testing

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