Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000410987 | SCV000489785 | uncertain significance | Multiple endocrine neoplasia type 2B | 2016-02-12 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000412050 | SCV000489786 | uncertain significance | Multiple endocrine neoplasia type 2A | 2016-02-12 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000474558 | SCV000543844 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1048 of the RET protein (p.Leu1048Val). This variant is present in population databases (rs774347808, gnomAD 0.003%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 22648184). ClinVar contains an entry for this variant (Variation ID: 372080). 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. |
| Ambry Genetics | RCV000574881 | SCV000674751 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-28 | criteria provided, single submitter | clinical testing | The p.L1048V variant (also known as c.3142C>G), located in coding exon 19 of the RET gene, results from a C to G substitution at nucleotide position 3142. The leucine at codon 1048 is replaced by valine, an amino acid with highly similar properties. This alteration has been reported in an individual with Hirschsprung disease (Carter TC et al. J. Hum. Genet., 2012 Aug;57:485-93). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Gene |
RCV003235199 | SCV003933570 | uncertain significance | not provided | 2022-12-13 | 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; Observed in an individual with Hirschprung disease (Carter et al., 2012); This variant is associated with the following publications: (PMID: 22648184, 14633923, 30034242, 29617658) |
| All of Us Research Program, |
RCV000474558 | SCV004822638 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-12-01 | criteria provided, single submitter | clinical testing | This missense variant replaces leucine with valine at codon 1048 of the RET 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 RET-related cancers in the literature. This variant has been identified in 5/251468 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. |
| Baylor Genetics | RCV004567898 | SCV005054209 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2024-01-14 | criteria provided, single submitter | clinical testing |