ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.448G>A (p.Val150Met)

gnomAD frequency: 0.00004  dbSNP: rs542980860
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000562589 SCV000674972 uncertain significance Hereditary cancer-predisposing syndrome 2023-01-17 criteria provided, single submitter clinical testing The p.V150M variant (also known as c.448G>A), located in coding exon 4 of the SDHA gene, results from a G to A substitution at nucleotide position 448. The valine at codon 150 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000695590 SCV000824100 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-11-21 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 150 of the SDHA protein (p.Val150Met). This variant is present in population databases (rs542980860, 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: 486371). 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 RCV000764601 SCV000895698 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
Laboratory of Molecular and Cytogenetics, Department of Anatomy, All India Institute of Medical Sciences (AIIMS) RCV003328100 SCV004035056 uncertain significance Multiple endocrine neoplasia type 2A 2023-06-10 criteria provided, single submitter clinical testing
Baylor Genetics RCV003471904 SCV004200597 uncertain significance Dilated cardiomyopathy 1GG 2023-08-18 criteria provided, single submitter clinical testing
GeneDx RCV004719886 SCV005325275 uncertain significance not provided 2023-12-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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