ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.428C>T (p.Thr143Met)

dbSNP: rs200675907
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000471253 SCV000553883 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 143 of the SDHA protein (p.Thr143Met). This variant is present in population databases (rs200675907, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of SDHA-related conditions (PMID: 34750850). ClinVar contains an entry for this variant (Variation ID: 412367). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SDHA protein function. Experimental studies have shown that this missense change affects SDHA function (PMID: 28724664). 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 RCV001022221 SCV001183932 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-01 criteria provided, single submitter clinical testing The p.T143M variant (also known as c.428C>T), located in coding exon 4 of the SDHA gene, results from a C to T substitution at nucleotide position 428. The threonine at codon 143 is replaced by methionine, an amino acid with similar properties. Functional studies in yeast demonstrated that this variant impairs SDHA activity (Bannon AE et al. Clin Cancer Res, 2017 Nov;23:6733-6743). This amino acid position is highly conserved in available vertebrate species. 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.
Genetic Services Laboratory, University of Chicago RCV001821297 SCV002067823 uncertain significance not specified 2019-12-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV003476129 SCV004202410 uncertain significance Dilated cardiomyopathy 1GG 2023-09-27 criteria provided, single submitter clinical testing

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