Total submissions: 15
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000724797 | SCV000228518 | uncertain significance | not provided | 2017-03-08 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000724797 | SCV000237614 | likely benign | not provided | 2019-10-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000539580 | SCV000643747 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-12-19 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000724797 | SCV000884809 | likely benign | not provided | 2018-06-20 | criteria provided, single submitter | clinical testing | The c.73768C>G; p.Pro24590Ala variant does not alter the amino acid sequence of the TTN protein and computational splice site prediction algorithms do not predict a change in the nearest splice site or creation of a cryptic splice site. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.04 % (identified on 115 out of 276,066 chromosomes), and evidence suggests that the vast majority of rare non-truncating TTN variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the c.73768C>G variant is likely to be benign. This variant was detected in an unaffected individual who was an obligate heterozygote for Barth syndrome and in whom a pathogenic TAZ variant was detected. Thus, this TTN variant is considered likely benign. |
CHEO Genetics Diagnostic Laboratory, |
RCV000769926 | SCV000901352 | benign | Cardiomyopathy | 2023-03-14 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics Inc | RCV000724797 | SCV001146507 | likely benign | not provided | 2019-03-13 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000724797 | SCV001152722 | likely benign | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | TTN: BP4, BS2 |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000259190 | SCV001519583 | likely benign | not specified | 2022-09-26 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.73768C>G (p.Pro24590Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00035 in 248182 control chromosomes, predominantly at a frequency of 0.0006 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.54 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.73768C>G has been reported in the literature in individuals affected with hypertrophic cardiomyopathy (Lopes_2013) and Brugada syndrome, but without echocardiographic evidence for structural heart disease (Mademont-Soler_2017). These reports do not provide unequivocal conclusions about association of the variant with DCM. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as VUS (n=3) or likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign. |
Mayo Clinic Laboratories, |
RCV000724797 | SCV001714638 | uncertain significance | not provided | 2021-12-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002345607 | SCV002652895 | likely benign | Cardiovascular phenotype | 2019-10-11 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Revvity Omics, |
RCV000724797 | SCV003826653 | likely benign | not provided | 2023-05-03 | criteria provided, single submitter | clinical testing | |
Clinical Genetics, |
RCV000724797 | SCV001921433 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000724797 | SCV001929807 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000724797 | SCV001953609 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000724797 | SCV001970705 | likely benign | not provided | no assertion criteria provided | clinical testing |