Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000163037 | SCV000213527 | likely benign | Hereditary cancer-predisposing syndrome | 2015-11-08 | 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. |
Counsyl | RCV000410355 | SCV000489673 | likely benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2016-11-03 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001080702 | SCV000555969 | likely benign | Hereditary nonpolyposis colorectal neoplasms | 2024-01-05 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000163037 | SCV000689800 | likely benign | Hereditary cancer-predisposing syndrome | 2017-08-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175374 | SCV000696104 | likely benign | not specified | 2019-06-06 | criteria provided, single submitter | clinical testing | Variant summary: MLH1 c.1284T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 2e-05 in 251332 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.1284T>C, has been reported in the literature in one individual affected with epithelial ovarian cancer (Pal_2012). The report does not provide unequivocal conclusions about association of the variant with Lynch Syndrome. One co-occurrence with another pathogenic MLH1 variant have been reported (c.1772_1775delATAG , p.Asp591fsX24), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586026 | SCV000888175 | likely benign | not provided | 2017-11-02 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000586026 | SCV001856941 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000163037 | SCV002528635 | likely benign | Hereditary cancer-predisposing syndrome | 2021-05-31 | criteria provided, single submitter | curation | |
CHEO Genetics Diagnostic Laboratory, |
RCV003149996 | SCV003838016 | likely benign | Breast and/or ovarian cancer | 2021-11-27 | criteria provided, single submitter | clinical testing | |
Myriad Genetics, |
RCV000410355 | SCV004018107 | benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-03-13 | criteria provided, single submitter | clinical testing | This variant is considered benign. This variant is a silent/synonymous amino acid change and it is not expected to impact splicing. |
Prevention |
RCV003952814 | SCV004771747 | likely benign | MLH1-related disorder | 2019-11-27 | 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). |
All of Us Research Program, |
RCV003995226 | SCV004840990 | likely benign | Lynch syndrome | 2023-11-30 | criteria provided, single submitter | clinical testing |