Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040371 | SCV000064062 | uncertain significance | not specified | 2012-07-31 | criteria provided, single submitter | clinical testing | The Ile15812Thr variant in TTN has been identified in 1/28 Spanish chromosomes a nd 1/196 Italian chromosomes from broad populations by the 1000 Genomes project (dbSNP rs72646819). The affected amino acid is not well conserved in evolution, suggesting that a change may be tolerated. Other computational analyses (biochem ical amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide stron g support for or against an impact to the protein. Additional information is nee ded to fully assess the clinical significance of this variant. |
Gene |
RCV000726968 | SCV000237312 | likely benign | not provided | 2020-11-03 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 30847666) |
Labcorp Genetics |
RCV000555854 | SCV000643373 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-06-06 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000726968 | SCV000704566 | uncertain significance | not provided | 2017-01-08 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000764327 | SCV000895346 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J; Tibial muscular dystrophy; Myopathy, myofibrillar, 9, with early respiratory failure; Early-onset myopathy with fatal cardiomyopathy; Hypertrophic cardiomyopathy 9 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000726968 | SCV001152873 | uncertain significance | not provided | 2023-11-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040371 | SCV001821374 | uncertain significance | not specified | 2021-08-23 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.47435T>C (p.Ile15812Thr) results in a non-conservative amino acid change located in the A-band of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 7e-05 in 241606 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (7e-05 vs 0.00039), allowing no conclusion about variant significance. c.47435T>C has been reported in the literature in individuals affected with Dilated Cardiomyopathy, sudden cardiac death, unspecified cardiomyopathies, or Left Ventricular Non-Compaction (Pugh_2014, Campuzano_2015, vanLint_2019, Vershinina_2020). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |