ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.64C>T (p.Leu22Phe)

gnomAD frequency: 0.00001  dbSNP: rs1473438869
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000526806 SCV000641448 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2023-08-29 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 22 of the SDHC protein (p.Leu22Phe). This variant is not present in population databases (gnomAD no frequency). 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: 465978). 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 phenylalanine 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.
Counsyl RCV000663232 SCV000786434 uncertain significance Paragangliomas 3 2018-04-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV001025343 SCV001187516 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-15 criteria provided, single submitter clinical testing The p.L22F variant (also known as c.64C>T), located in coding exon 2 of the SDHC gene, results from a C to T substitution at nucleotide position 64. The leucine at codon 22 is replaced by phenylalanine, an amino acid with highly similar properties. This amino acid position is highly 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 RCV001764571 SCV002000036 uncertain significance not provided 2023-05-19 criteria provided, single submitter clinical testing Not observed at 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
Myriad Genetics, Inc. RCV000663232 SCV004045384 uncertain significance Paragangliomas 3 2023-04-24 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV004568820 SCV005056661 uncertain significance Gastrointestinal stromal tumor 2024-01-19 criteria provided, single submitter clinical testing

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