ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.235A>G (p.Met79Val)

dbSNP: rs781702725
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001015284 SCV001176101 uncertain significance Hereditary cancer-predisposing syndrome 2022-04-25 criteria provided, single submitter clinical testing The p.M79V variant (also known as c.235A>G), located in coding exon 2 of the SDHAF2 gene, results from an A to G substitution at nucleotide position 235. The methionine at codon 79 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001211466 SCV001383007 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-12-06 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 79 of the SDHAF2 protein (p.Met79Val). This variant is present in population databases (rs781702725, gnomAD 0.0009%). 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: 821150). 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.
Baylor Genetics RCV003473576 SCV004202937 uncertain significance Paragangliomas 2 2023-09-17 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001211466 SCV004822156 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-04-03 criteria provided, single submitter clinical testing This missense variant replaces methionine with valine at codon 79 of the SDHAF2 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHAF2-related disorders in the literature. This variant has been identified in 1/249344 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV004768779 SCV005376345 uncertain significance not provided 2023-10-16 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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