ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1717C>G (p.Leu573Val)

gnomAD frequency: 0.00001  dbSNP: rs1445945083
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000702338 SCV000831190 uncertain significance Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2025-01-08 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 573 of the SDHA protein (p.Leu573Val). This variant is not present in population databases (gnomAD no frequency). 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: 579129). 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%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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 RCV002397461 SCV002712329 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-31 criteria provided, single submitter clinical testing The p.L573V variant (also known as c.1717C>G), located in coding exon 13 of the SDHA gene, results from a C to G substitution at nucleotide position 1717. The leucine at codon 573 is replaced by valine, 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV003153817 SCV003843039 uncertain significance Paragangliomas 5 2023-02-15 criteria provided, single submitter clinical testing The SDHA c.1717C>G (p.Leu573Val) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with SDHA-associated tumors. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Baylor Genetics RCV003472238 SCV004200651 uncertain significance Dilated cardiomyopathy 1GG 2023-05-12 criteria provided, single submitter clinical testing

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