ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.497T>G (p.Leu166Arg)

dbSNP: rs1571899223
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000823450 SCV000964310 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2022-10-23 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SDHC protein function. ClinVar contains an entry for this variant (Variation ID: 665216). This missense change has been observed in individual(s) with SDHC-related conditions (PMID: 21520333). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 166 of the SDHC protein (p.Leu166Arg).
Ambry Genetics RCV002345910 SCV002645612 likely pathogenic Hereditary cancer-predisposing syndrome 2023-08-11 criteria provided, single submitter clinical testing The p.L166R variant (also known as c.497T>G), located in coding exon 6 of the SDHC gene, results from a T to G substitution at nucleotide position 497. The leucine at codon 166 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been observed in multiple individuals with a personal and/or family history that is consistent with SDHC-related disease (Ambry internal data; Shi C. et al. Journal of the Endocrine Society, 2023 Sep;7(9)). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.

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