Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000409178 | SCV000489755 | uncertain significance | Multiple endocrine neoplasia, type 2b | 2015-12-01 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000410477 | SCV000489756 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2015-12-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000704852 | SCV000833823 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 830 of the RET protein (p.Gly830Arg). This variant is present in population databases (rs200127630, gnomAD 0.05%). This missense change has been observed in individual(s) with Hirschsprung disease (PMID: 22174939). ClinVar contains an entry for this variant (Variation ID: 372078). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 | RCV002429338 | SCV002742233 | benign | Hereditary cancer-predisposing syndrome | 2022-04-19 | 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. |
Fulgent Genetics, |
RCV002505998 | SCV002814675 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia, type 2b; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia, type 2a | 2022-03-09 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000410477 | SCV004018056 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2023-04-17 | 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. |
Prevention |
RCV003409569 | SCV004106401 | uncertain significance | RET-related condition | 2022-12-28 | criteria provided, single submitter | clinical testing | The RET c.2488G>A variant is predicted to result in the amino acid substitution p.Gly830Arg. This variant was reported in an individual with Hirschsprung disease (Table S4, So et al. 2011. PubMed ID: 22174939), however in another study, this variant was only detected in the control group (Supplementary Table 4, Tang et al. 2018. PubMed ID: 30217742). This variant is reported in 0.071% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-43615074-G-A). In ClinVar, this variant has conflicting interpretations, ranging from benign to uncertain (https://www.ncbi.nlm.nih.gov/clinvar/variation/372078). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |