Submissions for variant NM_003001.5(SDHC):c.32G>T (p.Arg11Leu)

dbSNP: rs767802663

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000167052	SCV000217879	uncertain significance	Hereditary cancer-predisposing syndrome	2023-12-06	criteria provided, single submitter	clinical testing	The p.R11L variant (also known as c.32G>T), located in coding exon 2 of the SDHC gene, results from a G to T substitution at nucleotide position 32. The arginine at codon 11 is replaced by leucine, an amino acid with dissimilar properties. This amino acid position is well 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000477280	SCV000546040	uncertain significance	Gastrointestinal stromal tumor; Paragangliomas 3	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 11 of the SDHC protein (p.Arg11Leu). This variant is present in population databases (rs767802663, gnomAD 0.004%). 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: 187333). 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 tolerated. 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.
GeneDx	RCV001657929	SCV001873973	uncertain significance	not provided	2023-11-06	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 30877234)
Sema4, Sema4	RCV000167052	SCV002527108	uncertain significance	Hereditary cancer-predisposing syndrome	2021-07-04	criteria provided, single submitter	curation
Baylor Genetics	RCV003474886	SCV004203054	uncertain significance	Gastrointestinal stromal tumor	2023-10-10	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003995552	SCV004840032	uncertain significance	Hereditary pheochromocytoma-paraganglioma	2023-11-02	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with leucine at codon 11 of the SDHC protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 SDHC-related disorders in the literature. This variant has been identified in 6/248946 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.