Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000205855 | SCV000260662 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 844 of the RET protein (p.Arg844Gln). This variant is present in population databases (rs55947360, gnomAD 0.01%). This missense change has been observed in individual(s) with familial medullary thyroid carcinoma (PMID: 18058472, 24699901, 25425582, 30877234). ClinVar contains an entry for this variant (Variation ID: 24951). 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 tolerated. Experimental studies have shown that this missense change does not substantially affect RET function (PMID: 29625052). 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 | RCV000575953 | SCV000674814 | benign | Hereditary cancer-predisposing syndrome | 2023-06-21 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Counsyl | RCV000662363 | SCV000784750 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2017-01-25 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000662363 | SCV000838404 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV001292765 | SCV001481411 | uncertain significance | Familial medullary thyroid carcinoma | 2020-12-22 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Gene |
RCV001574570 | SCV001801417 | uncertain significance | not provided | 2023-07-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Published functional studies demonstrate no damaging effect: RET kinase activity similar to wildtype (Huang et al., 2018); Observed in individuals with medullary thyroid cancer or breast cancer (Paszko et al., 2007; Guindalini et al., 2022) and co-observed with a pathogenic FH variant in an individual with pheochromocytoma (Ben Aim et al., 2019); This variant is associated with the following publications: (PMID: 20497437, 18058472, 26678667, 27014708, 21479187, 29590403, 25824727, 24699901, 9506724, 19469690, 29386230, 25425582, 34426522, 14633923, 29625052, 30877234, 35264596) |
Mayo Clinic Laboratories, |
RCV001574570 | SCV002541061 | uncertain significance | not provided | 2021-04-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001574570 | SCV002585215 | uncertain significance | not provided | 2022-09-01 | criteria provided, single submitter | clinical testing | RET: PS4:Moderate, PM2:Supporting, BS3:Supporting |
St. |
RCV000662363 | SCV003928100 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2023-04-03 | criteria provided, single submitter | clinical testing | The RET c.2531G>A (p.Arg844Gln) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a deleterious effect on protein function, however functional studies have demonstrated no damaging effect on RET function (PMID: 29625052). This variant has been reported in individuals with medullary thyroid cancer (PMID: 18058472) and pheochromocytoma (PMID: 35189708). In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Myriad Genetics, |
RCV000662363 | SCV004018474 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2023-04-18 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Baylor Genetics | RCV003466869 | SCV004208661 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2023-10-13 | criteria provided, single submitter | clinical testing |