Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000202914 | SCV000258170 | uncertain significance | Multiple endocrine neoplasia | 2015-02-13 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000410377 | SCV000489733 | uncertain significance | Multiple endocrine neoplasia type 2B | 2015-11-21 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000411486 | SCV000489734 | uncertain significance | Multiple endocrine neoplasia type 2A | 2015-11-21 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000462996 | SCV000543817 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 754 of the RET protein (p.Thr754Met). This variant is present in population databases (rs181856591, gnomAD 0.02%). 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: 135177). 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. |
Ambry Genetics | RCV000573705 | SCV000674805 | likely benign | Hereditary cancer-predisposing syndrome | 2023-04-19 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
Sema4, |
RCV000573705 | SCV002529969 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-02 | criteria provided, single submitter | curation | |
Fulgent Genetics, |
RCV002492438 | SCV002787858 | uncertain significance | Hirschsprung disease, susceptibility to, 1; Multiple endocrine neoplasia type 2B; Pheochromocytoma; Familial medullary thyroid carcinoma; Multiple endocrine neoplasia type 2A | 2024-04-29 | criteria provided, single submitter | clinical testing | |
Gene |
RCV003151746 | SCV003840662 | uncertain significance | not provided | 2024-09-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified in healthy individuals undergoing whole genome sequencing (PMID: 24728327); This variant is associated with the following publications: (PMID: 24336963, 24728327, 14633923) |
Baylor Genetics | RCV003460858 | SCV004208684 | uncertain significance | Hirschsprung disease, susceptibility to, 1 | 2024-03-15 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000462996 | SCV004838666 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2024-08-13 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with methionine at codon 754 of the RET protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 hereditary cancer in the literature. This variant has been identified in 6/251422 chromosomes 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. |
Neuberg Centre For Genomic Medicine, |
RCV004771463 | SCV005382284 | uncertain significance | Familial medullary thyroid carcinoma | 2023-05-20 | criteria provided, single submitter | clinical testing | The observed missense variant c.2261C>T (p.Thr754Met) in the RET gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with the allele frequency 0.002% in the gnomAD Exomes. This variant has been reported to the ClinVar database as Uncertain Significance. However, no details are available for independent assessment. The amino acid Threonine at position 754 is changed to a Methionine changing protein sequence and it might alter its composition and physico- chemical properties. Multiple lines of computational evidence (Polyphen - Probably damaging, SIFT - Damaging and MutationTaster - Disease causing) predict a damaging effect on protein structure and function for this variant. The residue is conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance. |
ITMI | RCV000121979 | SCV000086189 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |