Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000163869 | SCV000214456 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-10 | criteria provided, single submitter | clinical testing | The p.L5F variant (also known as c.15G>T), located in coding exon 1 of the SDHC gene, results from a G to T substitution at nucleotide position 15. The leucine at codon 5 is replaced by phenylalanine, an amino acid with highly similar properties. Based on protein sequence alignment, this amino acid position is well 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. |
| Illumina Laboratory Services, |
RCV000367287 | SCV000350260 | uncertain significance | Hereditary pheochromocytoma-paraganglioma | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000465397 | SCV000546030 | uncertain significance | Gastrointestinal stromal tumor; Paragangliomas 3 | 2024-01-28 | 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 5 of the SDHC protein (p.Leu5Phe). This variant is present in population databases (rs771746264, 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: 184591). 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. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000986017 | SCV001134810 | uncertain significance | not provided | 2020-08-28 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000986017 | SCV001769546 | uncertain significance | not provided | 2020-12-01 | criteria provided, single submitter | clinical testing | Not observed at a significant frequency in large population cohorts (Lek 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Baylor Genetics | RCV003474850 | SCV004203059 | uncertain significance | Gastrointestinal stromal tumor | 2023-09-27 | criteria provided, single submitter | clinical testing |