Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000041336 | SCV000065029 | benign | not specified | 2012-02-09 | criteria provided, single submitter | clinical testing | Ala617Ala in exon 11 of LMNA: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 0.4% (16/3738) African American chromosomes by the NHLBI Exome Sequencing Project in a broad population (http://evs.gs.washington.edu/EVS; dbSNP rs143189394). |
Invitae | RCV000234314 | SCV000291555 | benign | Charcot-Marie-Tooth disease, type 2 | 2019-12-31 | criteria provided, single submitter | clinical testing | |
EGL Genetic Diagnostics, |
RCV000041336 | SCV000338848 | benign | not specified | 2016-07-27 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000041336 | SCV000513501 | benign | not specified | 2015-04-16 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Genetic Services Laboratory, |
RCV000041336 | SCV000595614 | uncertain significance | not specified | 2013-02-08 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769733 | SCV000901155 | benign | Cardiomyopathy | 2015-10-09 | criteria provided, single submitter | clinical testing | |
Color | RCV000769733 | SCV000913460 | benign | Cardiomyopathy | 2018-03-23 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000041336 | SCV000917593 | benign | not specified | 2018-05-29 | criteria provided, single submitter | clinical testing | Variant summary: LMNA c.1851C>T 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 is found at a frequency of 0.000448 in the gnomAD database, but was observed predominantly in the African subpopulation at a frequency of 0.005139. The observed variant frequency within African control individuals in the gnomAD database is more than 20 fold above the estimated maximal expected allele frequency for a pathogenic variant in LMNA causing Cardiomyopathy phenotype (0.005139 vs. 0.00025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. c.1851C>T has been reported in the literature, however this report does not provide unequivocal conclusions about association of the variant with Cardiomyopathy. 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 and all classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign. |
Molecular Genetics Laboratory, |
RCV001173409 | SCV001336497 | likely benign | Charcot-Marie-Tooth disease | criteria provided, single submitter | clinical testing |