ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1591G>A (p.Val531Met)

gnomAD frequency: 0.00009  dbSNP: rs371056571
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000193391 SCV000248837 uncertain significance not specified 2015-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000226464 SCV000288118 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 531 of the SDHA protein (p.Val531Met). This variant is present in population databases (rs371056571, gnomAD 0.05%). 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: 212143). 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.
Counsyl RCV000410380 SCV000488010 uncertain significance Paragangliomas 5 2015-12-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV000573905 SCV000674957 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-23 criteria provided, single submitter clinical testing The p.V531M variant (also known as c.1591G>A), located in coding exon 12 of the SDHA gene, results from a G to A substitution at nucleotide position 1591. The valine at codon 531 is replaced by methionine, an amino acid with highly 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.
GeneDx RCV001093473 SCV001829286 uncertain significance not provided 2024-04-19 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in a pediatric patient with an unspecified cancer (PMID: 30455982); This variant is associated with the following publications: (PMID: 30455982)
Sema4, Sema4 RCV000573905 SCV002527725 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-13 criteria provided, single submitter curation
Myriad Genetics, Inc. RCV000410380 SCV004045351 uncertain significance Paragangliomas 5 2023-04-24 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV004567397 SCV005056594 uncertain significance Dilated cardiomyopathy 1GG 2023-11-29 criteria provided, single submitter clinical testing

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