Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000808226 | SCV000948322 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2018-10-25 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. 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. This variant has not been reported in the literature in individuals with TTN-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces serine with asparagine at codon 35106 of the TTN protein (p.Ser35106Asn). There is a small physicochemical difference between serine and asparagine. |
Ambry Genetics | RCV002406808 | SCV002669563 | uncertain significance | Cardiovascular phenotype | 2020-07-30 | criteria provided, single submitter | clinical testing | The p.S26041N variant (also known as c.78122G>A), located in coding exon 185 of the TTN gene, results from a G to A substitution at nucleotide position 78122. The serine at codon 26041 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is poorly 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. |