Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154963 | SCV000204645 | likely benign | not specified | 2014-07-14 | criteria provided, single submitter | clinical testing | Ala9447Thr in exon 122 of TTN: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, multiple mammals (marmoset, pig, black fly fox, megabat, and elephant) have a threonine (Thr) at this position despite high nearby amino acid conservation. It has also been identified in 3/3716 African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs371452173). |
Eurofins Ntd Llc |
RCV000724173 | SCV000225730 | uncertain significance | not provided | 2018-02-26 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001087214 | SCV000555502 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000724173 | SCV000979051 | likely benign | not provided | 2018-04-23 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000154963 | SCV002074530 | likely benign | not specified | 2022-01-04 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.28339G>A (p.Ala9447Thr) results in a non-conservative amino acid change in the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 248638 control chromosomes, predominantly at a frequency of 0.00073 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.28339G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (likely benign n=2, VUS n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
Revvity Omics, |
RCV000724173 | SCV003822352 | uncertain significance | not provided | 2022-03-23 | criteria provided, single submitter | clinical testing |