Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000152509 | SCV000201685 | uncertain significance | not specified | 2013-11-11 | criteria provided, single submitter | clinical testing | The Gly1305Trp variant in TTN has not been previously reported in individuals wi th cardiomyopathy or in large population studies. Computational analyses (bioche mical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) sugge st that the Gly1305Trp variant may impact the protein, though this information i s not predictive enough to determine pathogenicity. Additional information is ne eded to fully assess the clinical significance of the Gly1305Trp variant |
Eurofins Ntd Llc |
RCV000725635 | SCV000701054 | uncertain significance | not provided | 2016-10-19 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000725635 | SCV000728635 | likely benign | not provided | 2019-07-22 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000643675 | SCV000765362 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-03 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000770150 | SCV000901576 | uncertain significance | Cardiomyopathy | 2016-07-21 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000152509 | SCV002014880 | uncertain significance | not specified | 2023-08-03 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.3913G>T (p.Gly1305Trp) results in a non-conservative amino acid change located in the near Z-disk region of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 6.4e-05 in 250082 control chromosomes (gnomAD). This frequency is not significantly higher than estimated for a pathogenic variant in TTN causing Dilated Cardiomyopathy (6.4e-05 vs 0.00039), allowing no conclusion about variant significance. c.3913G>T has been reported in the literature in at least one individual affected with familial atrial fibrillation (Maltese_2019). This report does 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. The following publication has been ascertained in the context of this evaluation (PMID: 31539150). Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=5) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ambry Genetics | RCV002345483 | SCV002620769 | uncertain significance | Cardiovascular phenotype | 2020-05-29 | criteria provided, single submitter | clinical testing | The p.G1259W variant (also known as c.3775G>T), located in coding exon 21 of the TTN gene, results from a G to T substitution at nucleotide position 3775. The glycine at codon 1259 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000725635 | SCV003822309 | uncertain significance | not provided | 2020-09-14 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000725635 | SCV004148213 | uncertain significance | not provided | 2022-06-01 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000725635 | SCV004225940 | uncertain significance | not provided | 2022-02-10 | criteria provided, single submitter | clinical testing | PP3 |