ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.476C>T (p.Pro159Leu)

gnomAD frequency: 0.00002  dbSNP: rs759827541
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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 RCV000219502 SCV000276107 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-03 criteria provided, single submitter clinical testing The p.P159L variant (also known as c.476C>T), located in coding exon 5 of the SDHA gene, results from a C to T substitution at nucleotide position 476. The proline at codon 159 is replaced by leucine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV000649409 SCV000771237 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 159 of the SDHA protein (p.Pro159Leu). This variant is present in population databases (rs759827541, gnomAD 0.004%). 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: 232064). 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. 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.
Baylor Genetics RCV003475022 SCV004200576 uncertain significance Dilated cardiomyopathy 1GG 2023-09-09 criteria provided, single submitter clinical testing

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