Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001081705 | SCV000166608 | likely benign | Multiple endocrine neoplasia, type 2 | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000163453 | SCV000214000 | likely benign | Hereditary cancer-predisposing syndrome | 2019-04-13 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
Laboratory for Molecular Medicine, |
RCV000455280 | SCV000540175 | uncertain significance | not specified | 2016-03-31 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Only reported in proband with renal agenesis; ExAC: 0.1% (9/11538) Latino; ClinVar: 2 VUS |
Eurofins Ntd Llc |
RCV000727068 | SCV000705348 | uncertain significance | not provided | 2017-02-28 | criteria provided, single submitter | clinical testing | |
St. |
RCV003153409 | SCV000890955 | uncertain significance | Multiple endocrine neoplasia, type 2a | 2022-01-03 | criteria provided, single submitter | clinical testing | The RET c.1699G>A (p.Asp567Asn) missense change has a maximum subpopulation frequency of 0.062% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant occurs in the extracellular calmodulin-like motif (CaLM) in the cysteine rich domain, recently described as the location of a novel 3D cluster of oncogenic mutations in RET (PMID: 36166639). The in silico tool REVEL predicts a deleterious effect on protein function, and a molecular dynamics assay of mutations in CaLM and showed that this variant affects the conformational integrity of the RET-Ca2+ ion complex, underlying oncogenic properties which are increased in the presence of ligands/co-receptors that facilitate dimerization (PMID: 36166639). An in-vivo study showed that this variant is potentially druggable after existing RET-TKIs drugs, selpercatinib and pralsetinib, were shown to suppress the growth of NIH3T3 cells expressing p.Asp567Asn similar to their effect on NIH3T3 cells expressing known pathogenic mutations (PMID: 36166639). To our knowledge, this variant has not been reported in the literature in individuals with multiple endocrine neoplasia type IIA or type IIB. 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. |
Illumina Laboratory Services, |
RCV001104478 | SCV001261345 | benign | Multiple endocrine neoplasia | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001104479 | SCV001261346 | likely benign | Hirschsprung disease, susceptibility to, 1 | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Laboratory Services, |
RCV001107242 | SCV001264382 | benign | Pheochromocytoma | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001107243 | SCV001264383 | uncertain significance | Renal hypodysplasia/aplasia 1 | 2019-04-19 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Gene |
RCV000727068 | SCV002499950 | likely benign | not provided | 2022-04-13 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 21490379, 27834349, 27884173, 14633923) |
Sema4, |
RCV000163453 | SCV002529942 | likely benign | Hereditary cancer-predisposing syndrome | 2022-02-08 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000455280 | SCV002550385 | uncertain significance | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Genetics and Molecular Pathology, |
RCV002272134 | SCV002556561 | uncertain significance | Familial medullary thyroid carcinoma | 2021-03-04 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000727068 | SCV003816116 | uncertain significance | not provided | 2020-10-20 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000727068 | SCV004042481 | likely benign | not provided | 2023-12-01 | criteria provided, single submitter | clinical testing | RET: BS2 |
Prevention |
RCV003965038 | SCV004777010 | likely benign | RET-related condition | 2024-02-12 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |