Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156462 | SCV000206181 | likely benign | not specified | 2019-02-13 | criteria provided, single submitter | clinical testing | The c.31910-9C>A variant in TTN is classified as likely benign because it has been identified in 0.095% (33/34446) of Latino chromosomes by gnomAD (https://gnomad.broadinstitute.org) and computational tools do not suggest an impact on splicing. ACMG/AMP Criteria applied: BS1, BP4. |
Labcorp Genetics |
RCV000468721 | SCV000555221 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-11-24 | criteria provided, single submitter | clinical testing | |
Center for Advanced Laboratory Medicine, |
RCV000852864 | SCV000995598 | likely benign | Cardiomyopathy | 2018-12-13 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001555162 | SCV001776529 | likely benign | not provided | 2020-08-05 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000156462 | SCV001821376 | benign | not specified | 2021-08-23 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.31910-9C>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. 4/4 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 0.00014 in 248766 control chromosomes, predominantly at a frequency of 0.00096 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 2.5-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 Latino origin. To our knowledge, no occurrence of c.31910-9C>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. A co-occurrence with a pathogenic variant has been reported (MYBPC3 c.1504C>T, p.Arg502Trp; Internal testing), providing supporting evidence for a benign role. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Genome- |
RCV001840192 | SCV002101231 | benign | Autosomal recessive limb-girdle muscular dystrophy type 2J | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840193 | SCV002101232 | benign | Myopathy, myofibrillar, 9, with early respiratory failure | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840194 | SCV002101233 | benign | Early-onset myopathy with fatal cardiomyopathy | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Genome- |
RCV001840191 | SCV002101234 | benign | Tibial muscular dystrophy | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004544454 | SCV004776149 | likely benign | TTN-related disorder | 2020-06-05 | no assertion criteria provided | 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). |