ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.448C>A (p.Gln150Lys)

dbSNP: rs773142195
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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 RCV001879733 SCV002144608 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2021-06-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals with SDHC-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces glutamine with lysine at codon 150 of the SDHC protein (p.Gln150Lys). The glutamine residue is weakly conserved and there is a small physicochemical difference between glutamine and lysine.
All of Us Research Program, National Institutes of Health RCV004009244 SCV004829666 uncertain significance Hereditary pheochromocytoma-paraganglioma 2023-05-16 criteria provided, single submitter clinical testing This missense variant replaces glutamine with lysine at codon 150 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 1/248560 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.
Ambry Genetics RCV004656697 SCV005161254 uncertain significance Hereditary cancer-predisposing syndrome 2024-06-22 criteria provided, single submitter clinical testing The p.Q150K variant (also known as c.448C>A), located in coding exon 6 of the SDHC gene, results from a C to A substitution at nucleotide position 448. The glutamine at codon 150 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

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