Total submissions: 25
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
International Society for Gastrointestinal Hereditary Tumours |
RCV000075170 | SCV000106161 | no known pathogenicity | Lynch syndrome | 2013-09-05 | reviewed by expert panel | research | Multifactorial likelihood analysis posterior probability <0.001 |
Gene |
RCV000679266 | SCV000149365 | likely benign | not provided | 2020-12-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16042583, 16438707, 20223024, 21056691, 25637381, 11524701, 19117025, 17510385, 10709098, 22949379, 11376800, 23741719, 15849733, 9326924, 24055113, 27153395, 26659639, 28526081, 21404117, 18383312, 29785566, 17192056, 32547938) |
Ambry Genetics | RCV000115456 | SCV000184608 | benign | Hereditary cancer-predisposing syndrome | 2019-01-17 | 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. |
Invitae | RCV001083668 | SCV000219061 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000202064 | SCV000539641 | uncertain significance | not specified | 2017-01-10 | 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: Two mammals and one non-mammal have a Thr at this position. It has a max MAF of 0.09% in gnomAD. It is reported in 7 papers in HGMD, classified as DM, most comments suggest VUS. It is classified in ClinVar with 3 stars as Benign by InSiGHT (expert panel) and Pathway genomics, and likely benign by GeneDx and Invitae, and as VUS by Mayo and CSER_CC_NCGL. |
Genetic Services Laboratory, |
RCV000202064 | SCV000595807 | benign | not specified | 2021-05-26 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000679266 | SCV000601351 | benign | not provided | 2022-11-11 | criteria provided, single submitter | clinical testing | |
Center for Human Genetics, |
RCV000659870 | SCV000781755 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000659870 | SCV000786114 | likely benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2018-02-28 | criteria provided, single submitter | clinical testing | |
Preventiongenetics, |
RCV000679266 | SCV000805947 | likely benign | not provided | 2017-04-03 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000679266 | SCV000884118 | benign | not provided | 2018-02-05 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000115456 | SCV000902604 | benign | Hereditary cancer-predisposing syndrome | 2015-10-15 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000659870 | SCV001136408 | benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000679266 | SCV001153842 | likely benign | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | MLH1: BP4, BS3:Supporting |
Illumina Laboratory Services, |
RCV000659870 | SCV001308772 | uncertain significance | Colorectal cancer, hereditary nonpolyposis, type 2 | 2018-03-29 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000202064 | SCV001737682 | benign | not specified | 2021-06-14 | criteria provided, single submitter | clinical testing | Variant summary: MLH1 c.1321G>A (p.Ala441Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00034 in 251274 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in MLH1 causing Hereditary Nonpolyposis Colorectal Cancer (0.00034 vs 0.00071), allowing no conclusion about variant significance. c.1321G>A has been reported in the literature in individuals affected with Hereditary Nonpolyposis Colorectal Cancer/Lynch syndrome (example Borg_2000, Cunningham_2001, Mangold_2005, Kurzawski_2006, South_2009). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer/Lynch syndrome. At-least two co-occurrences with other pathogenic variant(s) have been reported in the literature and observed in our laboratory (Borg_2000, BRCA1 3166insTGAGA; our laboratory, MSH6 c.999delC, p.Lys334fs), providing supporting evidence for a benign role. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant on mismatch repair activity (MMR). Multiple clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 with a majority consensus leaning towards benign/likely benign (n=11). Based on the overwhelming evidence supporting a non-actionable as outlined above, the variant was classified as benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV001798259 | SCV002042072 | likely benign | Breast and/or ovarian cancer | 2023-04-14 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000115456 | SCV002528638 | benign | Hereditary cancer-predisposing syndrome | 2021-03-04 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000202064 | SCV002760287 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV000115456 | SCV002819232 | benign | Hereditary cancer-predisposing syndrome | 2022-11-22 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000659870 | SCV004018204 | benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-03-16 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease. |
Pathway Genomics | RCV000144611 | SCV000189938 | benign | Lynch syndrome 1 | 2014-07-24 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148618 | SCV000190333 | uncertain significance | Colorectal cancer, non-polyposis | 2014-06-01 | no assertion criteria provided | research | |
Mayo Clinic Laboratories, |
RCV000202064 | SCV000257050 | uncertain significance | not specified | no assertion criteria provided | research | ||
True Health Diagnostics | RCV000115456 | SCV000788017 | likely benign | Hereditary cancer-predisposing syndrome | 2017-08-30 | no assertion criteria provided | clinical testing |