Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017116 | SCV001178146 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-06 | criteria provided, single submitter | clinical testing | The p.V347M variant (also known as c.1039G>A), located in coding exon 5 of the RET gene, results from a G to A substitution at nucleotide position 1039. The valine at codon 347 is replaced by methionine, an amino acid with highly similar properties. This alteration was identified in 1 individual in a cohort of patients with short-segment Hirschsprung disease and 0 controls. (Tang CS et al. Gastroenterology, 2018 Dec;155:1908-1922.e5). 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. |
| Labcorp Genetics |
RCV001860854 | SCV002300900 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 347 of the RET protein (p.Val347Met). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 30217742). ClinVar contains an entry for this variant (Variation ID: 822070). 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. |
| Baylor Genetics | RCV003461357 | SCV004206722 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-06-06 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004998548 | SCV005623053 | uncertain significance | not provided | 2024-01-02 | criteria provided, single submitter | clinical testing |