Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001079322 | SCV000284018 | benign | Hereditary nonpolyposis colorectal neoplasms | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000580704 | SCV000684742 | likely benign | Hereditary cancer-predisposing syndrome | 2015-10-16 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001818568 | SCV000696110 | benign | not specified | 2022-04-06 | criteria provided, single submitter | clinical testing | Variant summary: MLH1 c.1410-10T>G alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 8.4e-05 in 251424 control chromosomes, predominantly at a frequency of 0.0008 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 1.13 fold of the estimated maximal expected allele frequency for a pathogenic variant in MLH1 causing Hereditary Nonpolyposis Colorectal Cancer/Lynch Syndrome phenotype (0.00071), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1410-10T>G has been reported in the literature as a VUS in individuals with colorectal cancer (example, Poynter_2008, Guindalini_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer/Lynch Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV000586910 | SCV001941704 | benign | not provided | 2015-03-03 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV001818568 | SCV002071324 | likely benign | not specified | 2020-02-27 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000580704 | SCV002528648 | benign | Hereditary cancer-predisposing syndrome | 2020-10-01 | criteria provided, single submitter | curation | |
KCCC/NGS Laboratory, |
RCV003316241 | SCV004015882 | likely benign | Colorectal cancer, hereditary nonpolyposis, type 2 | 2023-07-07 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003491995 | SCV004240740 | likely benign | Breast and/or ovarian cancer | 2023-06-29 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV003998739 | SCV004815008 | likely benign | Lynch syndrome | 2024-02-05 | criteria provided, single submitter | clinical testing |