Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000206385 | SCV000261281 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 963 of the RET protein (p.Leu963Ile). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with RET-related conditions. ClinVar contains an entry for this variant (Variation ID: 220609). 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 disruptive. 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 | RCV000662412 | SCV000784843 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2016-12-27 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV001016859 | SCV001177858 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-28 | criteria provided, single submitter | clinical testing | The p.L963I variant (also known as c.2887C>A), located in coding exon 17 of the RET gene, results from a C to A substitution at nucleotide position 2887. The leucine at codon 963 is replaced by isoleucine, 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. |
| Gene |
RCV003441786 | SCV004167915 | uncertain significance | not provided | 2023-10-11 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); 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; This variant is associated with the following publications: (PMID: 14633923) |
| Baylor Genetics | RCV003462384 | SCV004208719 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-08-06 | criteria provided, single submitter | clinical testing |