Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000732211 | SCV000860134 | uncertain significance | not provided | 2018-03-15 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001307848 | SCV001497276 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 34133 of the TTN protein (p.Ile34133Thr). This variant is present in population databases (rs764179161, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 596390). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222619 | SCV002500287 | uncertain significance | not specified | 2022-03-09 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.94694T>C (p.Ile31565Thr) results in a non-conservative amino acid change located in the M-band region (100% PSI score, corresponding to a constitutively expressed exon) 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 3.6e-05 in 249066 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.94694T>C has been reported in the literature as a VUS in an asymptomatic (incidental) male with no FH of cardiomyopathy and an asymmetric septal pattern of hypertrophy who underwent whole genome analysis (WGS) following prior genetic testing on a 46 gene panel that had not established a molecular diagnosis (example, Bagnall_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hypertrophic/Dilated Cardiomyopathy/Limb-Girdle Muscular Dystrophy, Type 2J. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two 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. |
Revvity Omics, |
RCV000732211 | SCV003819742 | uncertain significance | not provided | 2022-08-22 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004535854 | SCV004735283 | uncertain significance | TTN-related disorder | 2023-11-07 | no assertion criteria provided | clinical testing | The TTN c.102398T>C variant is predicted to result in the amino acid substitution p.Ile34133Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.021% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179398944-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |