Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000233343 | SCV000290564 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-07-29 | criteria provided, single submitter | clinical testing | 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: 241363). 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: "Tolerated"; 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. This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 176 of the RET protein (p.Ile176Met). |
All of Us Research Program, |
RCV000233343 | SCV004838431 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-03-05 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with methionine at codon 176 of the RET protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with RET-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV004020852 | SCV005028538 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.I176M variant (also known as c.528T>G), located in coding exon 3 of the RET gene, results from a T to G substitution at nucleotide position 528. The isoleucine at codon 176 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |