Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Biesecker Lab/Clinical Genomics Section, |
RCV000172177 | SCV000051101 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
Gene |
RCV000412704 | SCV000237858 | uncertain significance | not specified | 2014-08-18 | criteria provided, single submitter | 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-CRDM panel(s). |
Ambry Genetics | RCV000617797 | SCV000736891 | uncertain significance | Cardiovascular phenotype | 2017-08-08 | criteria provided, single submitter | clinical testing | The p.R23855Q variant (also known as c.71564G>A), located in coding exon 180 of the TTN gene, results from a G to A substitution at nucleotide position 71564. The arginine at codon 23855 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in 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. |
Invitae | RCV000687392 | SCV000814956 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-01-29 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with glutamine at codon 32920 of the TTN protein (p.Arg32920Gln). There is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs752015224, ExAC 0.02%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 191836). This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. 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. |
Fulgent Genetics, |
RCV002492723 | SCV002782502 | 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 | 2021-08-17 | criteria provided, single submitter | clinical testing | |
Institut für Laboratoriums- |
RCV000491239 | SCV000298139 | uncertain significance | Dilated cardiomyopathy 1S | 2016-05-01 | no assertion criteria provided | research |