Total submissions: 12
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000154937 | SCV000204619 | likely benign | not specified | 2015-10-31 | criteria provided, single submitter | clinical testing | p.Thr16970Ala in exon 247 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.5% (45/9792) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs200017524). |
Gene |
RCV000154937 | SCV000237346 | likely benign | not specified | 2018-01-11 | 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. |
Eurofins Ntd Llc |
RCV000154937 | SCV000335002 | likely benign | not specified | 2015-09-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001082823 | SCV000555270 | benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-29 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000622130 | SCV000736507 | likely benign | Cardiovascular phenotype | 2018-07-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
Athena Diagnostics | RCV000714058 | SCV000844724 | benign | not provided | 2018-07-20 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840144 | SCV002100420 | benign | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840145 | SCV002100422 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840146 | SCV002100423 | benign | Early-onset myopathy with fatal cardiomyopathy | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840143 | SCV002100424 | benign | Tibial muscular dystrophy | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000154937 | SCV004021274 | benign | not specified | 2023-06-12 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.50908A>G (p.Thr16970Ala) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00036 in 248186 control chromosomes, predominantly at a frequency of 0.0047 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 12-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. To our knowledge, no occurrence of c.50908A>G in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Seven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Prevention |
RCV004544424 | SCV004769340 | likely benign | TTN-related disorder | 2020-11-10 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |