Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000213289 | SCV000272694 | likely benign | not specified | 2018-11-09 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Gene |
RCV000726732 | SCV000617124 | likely benign | not provided | 2020-12-15 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 22526018, 23446887, 31983221) |
Invitae | RCV000548016 | SCV000643404 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-06-26 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000726732 | SCV000702564 | uncertain significance | not provided | 2016-10-14 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000768979 | SCV000900352 | uncertain significance | Cardiomyopathy | 2021-11-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000213289 | SCV001821373 | uncertain significance | not specified | 2021-08-23 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.49243G>A (p.Ala16415Thr) results in a non-conservative amino acid change located in the A-band domain 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 9.6e-05 in 249438 control chromosomes (gnomAD and publication data). This frequency is not significantly higher than expected for a pathogenic variant in TTN causing Dilated Cardiomyopathy (9.6e-05 vs 0.00039), allowing no conclusion about variant significance. c.49243G>A has been reported in the literature in individuals affected with Dilated cardiomyopathy, Hypertrophic cardiomyopathy and Muscular dystrophy as well as in one healthy control (Vasli_2012, Lopes_2013, Mazzarotto_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. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=4) and likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Ambry Genetics | RCV002433937 | SCV002746203 | uncertain significance | Cardiovascular phenotype | 2018-07-05 | criteria provided, single submitter | clinical testing | The p.A9918T variant (also known as c.29752G>A), located in coding exon 118 of the TTN gene, results from a G to A substitution at nucleotide position 29752. The alanine at codon 9918 is replaced by threonine, an amino acid with similar properties. This variant (reported as p.A16415T) was detected in the compound heterozygous state with TTN p.V998M (reported as p.V1034M) in a patient with limb girdle muscular dystrophy and her affected brother (Vasli N et al. Acta Neuropathol. 2012;124:273-83). This alteration was also identified in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Lopes LR et al. J. Med. Genet. 2013;50:228-39). This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Revvity Omics, |
RCV000726732 | SCV003821023 | uncertain significance | not provided | 2022-12-21 | criteria provided, single submitter | clinical testing | |
Clinical Genetics, |
RCV000726732 | SCV001925277 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Diagnostic Laboratory, |
RCV000726732 | SCV001963541 | uncertain significance | not provided | no assertion criteria provided | clinical testing |