ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.239T>C (p.Leu80Ser)

gnomAD frequency: 0.00005  dbSNP: rs376560419
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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 RCV000234685 SCV000290370 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-01-06 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 80 of the SDHAF2 protein (p.Leu80Ser). This variant is present in population databases (rs376560419, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 241216). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV000569293 SCV000675045 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-22 criteria provided, single submitter clinical testing The p.L80S variant (also known as c.239T>C), located in coding exon 2 of the SDHAF2 gene, results from a T to C substitution at nucleotide position 239. The leucine at codon 80 is replaced by serine, 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.
GeneDx RCV002307466 SCV002601141 uncertain significance not provided 2024-08-19 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; This variant is associated with the following publications: (PMID: 30552426)
Baylor Genetics RCV004567755 SCV005056619 uncertain significance Paragangliomas 2 2023-11-09 criteria provided, single submitter clinical testing

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