Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000823912 | SCV000964783 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-05-22 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 857 of the RET protein (p.Gln857His). 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: 665594). 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. |
| Prevention |
RCV004538130 | SCV004106889 | uncertain significance | RET-related disorder | 2023-10-03 | criteria provided, single submitter | clinical testing | The RET c.2571G>T variant is predicted to result in the amino acid substitution p.Gln857His. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. In ClinVar, this variant is classified as having uncertain clinical significance (https://www.ncbi.nlm.nih.gov/clinvar/variation/665594/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
| Ambry Genetics | RCV004659238 | SCV005157004 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-05-29 | criteria provided, single submitter | clinical testing | The p.Q857H variant (also known as c.2571G>T), located in coding exon 14 of the RET gene, results from a G to T substitution at nucleotide position 2571. The glutamine at codon 857 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |