Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000547644 | SCV000658484 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-06-04 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 155 of the RET protein (p.Pro155Gln). This variant is not present in population databases (gnomAD no frequency). 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: 477375). 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. |
| Ambry Genetics | RCV000568122 | SCV000674867 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-02-11 | criteria provided, single submitter | clinical testing | The p.P155Q variant (also known as c.464C>A), located in coding exon 3 of the RET gene, results from a C to A substitution at nucleotide position 464. The proline at codon 155 is replaced by glutamine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 10000 alleles tested) in our clinical cohort. 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. |
| Baylor Genetics | RCV003459265 | SCV004206699 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-07-06 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000547644 | SCV004833874 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-05-08 | criteria provided, single submitter | clinical testing |