Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000123314 | SCV000166621 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-04-08 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 136112). 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. This missense change has been observed in individual(s) with RET-related conditions (PMID: 26071011, 29850289, 33219105). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 898 of the RET protein (p.Asp898Tyr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. |
| Ambry Genetics | RCV001016327 | SCV001177272 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-12-16 | criteria provided, single submitter | clinical testing | The p.D898Y variant (also known as c.2692G>T), located in coding exon 15 of the RET gene, results from a G to T substitution at nucleotide position 2692. The aspartic acid at codon 898 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant has been reported in individuals reported to have multiple endocrine neoplasia type 2 (MEN2); however, specific clinical information was not provided (Lang BH et al. World J Surg, 2015 Oct;39:2484-91). This variant has also been reported in an individual with a pheochromocytoma and her sister with papillary thyroid cancer; however, their mother with papillary thyroid cancer did not carry this variant (Yi JW et al. Case Rep Endocrinol, 2018 Apr;2018:8657914). 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. |