ClinVar Miner

Submissions for variant NM_004168.4(SDHA):c.1304T>G (p.Leu435Arg)

dbSNP: rs1579409500
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001957990 SCV002210689 likely pathogenic Mitochondrial complex II deficiency, nuclear type 1; Paragangliomas 5 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 435 of the SDHA protein (p.Leu435Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with SDHA-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1438967). 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 expected to disrupt SDHA protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV002386771 SCV002693741 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-30 criteria provided, single submitter clinical testing The p.L435R variant (also known as c.1304T>G), located in coding exon 10 of the SDHA gene, results from a T to G substitution at nucleotide position 1304. The leucine at codon 435 is replaced by arginine, an amino acid with dissimilar 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.
Baylor Genetics RCV004571667 SCV005055640 uncertain significance Dilated cardiomyopathy 1GG 2024-01-04 criteria provided, single submitter clinical testing

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