Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000793359 | SCV000932707 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2021-01-15 | criteria provided, single submitter | clinical testing | This variant has been observed in an individual with clinical features of Hirschsprung disease (PMID: 8852653). ClinVar contains an entry for this variant (Variation ID: 135182). This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with glutamine at codon 1039 of the RET protein (p.Pro1039Gln). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and glutamine. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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 | RCV002321602 | SCV002607917 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-23 | criteria provided, single submitter | clinical testing | The p.P1039Q variant (also known as c.3116C>A), located in coding exon 19 of the RET gene, results from a C to A substitution at nucleotide position 3116. The proline at codon 1039 is replaced by glutamine, an amino acid with similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS One, 2014 Apr;9:e94554). 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. |
| ITMI | RCV000121984 | SCV000086195 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |