ClinVar Miner

Submissions for variant NM_017841.4(SDHAF2):c.331G>A (p.Glu111Lys)

gnomAD frequency: 0.00016  dbSNP: rs145616631
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000461728 SCV000552842 uncertain significance Hereditary pheochromocytoma-paraganglioma 2025-01-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 111 of the SDHAF2 protein (p.Glu111Lys). This variant is present in population databases (rs145616631, gnomAD 0.04%). 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: 411611). 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 RCV001019980 SCV001181400 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-10 criteria provided, single submitter clinical testing The p.E111K variant (also known as c.331G>A), located in coding exon 3 of the SDHAF2 gene, results from a G to A substitution at nucleotide position 331. The glutamic acid at codon 111 is replaced by lysine, an amino acid with similar 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.
Sema4, Sema4 RCV001019980 SCV002527232 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-04 criteria provided, single submitter curation
Baylor Genetics RCV003476105 SCV004202954 uncertain significance Paragangliomas 2 2024-03-06 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003477988 SCV004220252 likely benign not provided 2023-08-09 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003960039 SCV004773207 uncertain significance SDHAF2-related disorder 2024-02-15 no assertion criteria provided clinical testing The SDHAF2 c.331G>A variant is predicted to result in the amino acid substitution p.Glu111Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of African descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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