Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
CHEO Genetics Diagnostic Laboratory, |
RCV001170112 | SCV001332651 | benign | Familial thoracic aortic aneurysm and aortic dissection | 2018-01-17 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001446488 | SCV001649535 | likely benign | Aortic aneurysm, familial thoracic 7 | 2021-06-29 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001527010 | SCV001737823 | benign | not specified | 2021-05-24 | criteria provided, single submitter | clinical testing | Variant summary: MYLK c.5238+6G>A 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 0.00016 in 251472 control chromosomes, predominantly at a frequency of 0.0011 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 22-fold the estimated maximal expected allele frequency for a pathogenic variant in MYLK causing Thoracic Aortic Aneurysms And Dissections phenotype (5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.5238+6G>A in individuals affected with Thoracic Aortic Aneurysms And Dissections and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Both laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Gene |
RCV000865600 | SCV001796387 | likely benign | not provided | 2021-01-11 | criteria provided, single submitter | clinical testing |