ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.445T>C (p.Tyr149His)

dbSNP: rs2102385345
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001369437 SCV001565878 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2020-03-17 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SDHC-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with histidine at codon 149 of the SDHC protein (p.Tyr149His). The tyrosine residue is weakly conserved and there is a moderate physicochemical difference between tyrosine and histidine.
Ambry Genetics RCV002329383 SCV002635544 uncertain significance Hereditary cancer-predisposing syndrome 2020-10-05 criteria provided, single submitter clinical testing The p.Y149H variant (also known as c.445T>C), located in coding exon 6 of the SDHC gene, results from a T to C substitution at nucleotide position 445. The tyrosine at codon 149 is replaced by histidine, an amino acid with similar properties. This amino acid position is not 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.

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