ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.352A>G (p.Ile118Val)

gnomAD frequency: 0.00001  dbSNP: rs747994812
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020532 SCV001182023 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-22 criteria provided, single submitter clinical testing The p.I118V variant (also known as c.352A>G), located in coding exon 3 of the SDHAF2 gene, results from an A to G substitution at nucleotide position 352. The isoleucine at codon 118 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 RCV001067015 SCV001232044 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-08-07 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 823888). This variant has not been reported in the literature in individuals affected with SDHAF2-related conditions. This variant is present in population databases (rs747994812, gnomAD 0.003%). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 118 of the SDHAF2 protein (p.Ile118Val).
Institute of Human Genetics, University of Leipzig Medical Center RCV001253131 SCV001428681 uncertain significance Paragangliomas 2 2019-12-23 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV001067015 SCV004834955 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-10-06 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 118 of the SDHAF2 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 3/251486 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.

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