Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570468 | SCV000674885 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-03-17 | criteria provided, single submitter | clinical testing | The p.W1056* variant (also known as c.3167G>A), located in coding exon 19 of the RET gene, results from a G to A substitution at nucleotide position 3167. This changes the amino acid from a tryptophan to a stop codon within coding exon 19. Per ACMG guidelines this variant could be interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294); however, this truncation occurs at the 3' terminus of RET and removes only the last 59 amino acids of the protein. The exact functional impact of these amino acids is unknown at this time.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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV001853797 | SCV002200753 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-02-18 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 486334). This variant has not been reported in the literature in individuals affected with RET-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp1056*) in the RET gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 59 amino acid(s) of the RET protein. |