ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.205A>G (p.Ile69Val)

gnomAD frequency: 0.00001  dbSNP: rs753561812
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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 RCV000641921 SCV000763571 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2023-12-04 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 69 of the SDHC protein (p.Ile69Val). This variant is present in population databases (rs753561812, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 534376). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV002420748 SCV002725100 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-26 criteria provided, single submitter clinical testing The p.I69V variant (also known as c.205A>G), located in coding exon 4 of the SDHC gene, results from an A to G substitution at nucleotide position 205. The isoleucine at codon 69 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health RCV004003949 SCV004832956 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-04-10 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with valine at codon 69 of the SDHC protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with SDHC-related disorders in the literature. This variant has been identified in 3/248986 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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