ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.25G>A (p.Val9Ile)

gnomAD frequency: 0.00001  dbSNP: rs774768866
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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 RCV000234613 SCV000287797 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 9 of the SDHC protein (p.Val9Ile). This variant is present in population databases (rs774768866, gnomAD 0.04%). 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: 239451). 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 isoleucine 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 RCV002429110 SCV002743031 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-28 criteria provided, single submitter clinical testing The p.V9I variant (also known as c.25G>A), located in coding exon 2 of the SDHC gene, results from a G to A substitution at nucleotide position 25. The valine at codon 9 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is not well 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.
GeneDx RCV003227726 SCV003924788 uncertain significance not provided 2022-11-09 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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