Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040052 | SCV000063743 | uncertain significance | not specified | 2017-06-28 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Thr7599Met va riant in TTN has been identified by our laboratory in 1 Asian adult with HCM, 1 Ethiopian neonate with congenital HCM, and 2 Caucasian adults with DCM, of which 1 carried a likely pathogenic variant in another gene sufficient to explain the ir disease (Pugh 2014). Additionally, this variant has been identified in 0.1% ( 38/34342) of Latino chromosomes by the Genome Aggregation Database (gnomAD, http ://gnomad.broadinstitute.org/; dbSNP rs72648990) and has been reported in ClinVa r (Variation ID: 46782). Threonine (Thr) at position 7599 is not conserved in ma mmals or evolutionarily distant species, and one mammal (white rhinoceros) carri es a methionine (Met) at this position, raising the possibility that this change may be tolerated. Additional computational prediction tools do not provide stro ng support for or against an impact to the protein. In summary, while the clinic al significance of the p.Thr7599Met variant is uncertain, its frequency and lack of conservation suggest that it is more likely to be benign. |
Gene |
RCV000725012 | SCV000238377 | likely benign | not provided | 2021-02-22 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 24503780, 27066507) |
Labcorp Genetics |
RCV000226309 | SCV000286538 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-08-22 | criteria provided, single submitter | clinical testing | |
Eurofins Ntd Llc |
RCV000725012 | SCV000333200 | uncertain significance | not provided | 2018-07-03 | criteria provided, single submitter | clinical testing | |
Genomic Research Center, |
RCV004528205 | SCV000845366 | uncertain significance | TTN-related disorder | 2018-08-07 | criteria provided, single submitter | clinical testing | |
Athena Diagnostics | RCV000725012 | SCV001146357 | likely benign | not provided | 2019-12-30 | criteria provided, single submitter | clinical testing | |
Genetics and Genomics Program, |
RCV001293146 | SCV001434136 | uncertain significance | Hypertrophic cardiomyopathy | criteria provided, single submitter | research | ||
ARUP Laboratories, |
RCV000725012 | SCV002049659 | uncertain significance | not provided | 2021-02-24 | criteria provided, single submitter | clinical testing | The TTN c.26528C>T; p.Thr8843Met variant (rs72648990; ClinVar Variation ID: 46782) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Given the available evidence, the clinical significance of the p.Thr8843Met variant cannot be determined with certainty. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040052 | SCV002571829 | likely benign | not specified | 2022-08-06 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000725012 | SCV003826684 | likely benign | not provided | 2023-05-30 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000725012 | SCV004155242 | likely benign | not provided | 2023-07-01 | criteria provided, single submitter | clinical testing | TTN: BP4 |