Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001852408 | SCV002135727 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2023-07-31 | criteria provided, single submitter | clinical testing | 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. 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). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 35028 of the TTN protein (p.Thr35028Met). This variant is present in population databases (rs56001826, gnomAD 0.006%). 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: 203090). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. |
Fulgent Genetics, |
RCV002492845 | SCV002791237 | 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 | 2021-08-23 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004528967 | SCV004112612 | uncertain significance | TTN-related disorder | 2023-02-08 | criteria provided, single submitter | clinical testing | The TTN c.105083C>T variant is predicted to result in the amino acid substitution p.Thr35028Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0056% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179396259-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV000185113 | SCV000237938 | not provided | not provided | 2013-09-13 | no assertion provided | clinical testing | Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s). |
Clinical Genetics, |
RCV000185113 | SCV001918024 | uncertain significance | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000185113 | SCV001932082 | uncertain significance | not provided | no assertion criteria provided | clinical testing |