Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001083169 | SCV000286388 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Phosphorus, |
RCV000577970 | SCV000679938 | uncertain significance | Dilated cardiomyopathy 1G | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Phosphorus, |
RCV000578025 | SCV000679939 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Phosphorus, |
RCV000578101 | SCV000679940 | uncertain significance | Tibial muscular dystrophy | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000726929 | SCV000704209 | uncertain significance | not provided | 2016-12-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000726929 | SCV000730986 | likely benign | not provided | 2021-03-18 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 23396983) |
Ambry Genetics | RCV000619673 | SCV000737244 | likely benign | Cardiovascular phenotype | 2020-02-06 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000591543 | SCV001363829 | uncertain significance | not specified | 2023-05-01 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.10115-4G>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. 5/5 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 0.0001 (i.e., 25 carriers) in 249358 control chromosomes, predominantly at a frequency of 0.00013 (i.e., 15 carriers) within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Cardiomyopathy (0.0001 vs 0.00063), allowing no conclusion about variant significance. c.10115-4G>A has been reported in the literature in individuals affected with Cardiomyopathy and sudden unexplained death (SUD), however without strong evidence for causality (Campuzano_2015, Lopes_2013). These reports do 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. The following publications have been ascertained in the context of this evaluation (PMID: 26516846, 23396983). Five ClinVar submitters (evaluation after 2014) have cited the variant as either uncertain significance (n = 2) or likely benign (n = 3). Based on the evidence outlined above, the variant was classified as VUS. |
CHEO Genetics Diagnostic Laboratory, |
RCV003486779 | SCV004239809 | uncertain significance | Cardiomyopathy | 2023-03-20 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000726929 | SCV001743263 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics, |
RCV000591543 | SCV001919360 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000726929 | SCV001959616 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000726929 | SCV001969930 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000726929 | SCV002035488 | likely benign | not provided | no assertion criteria provided | clinical testing |