Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000621913 | SCV000737068 | uncertain significance | Cardiovascular phenotype | 2016-02-12 | criteria provided, single submitter | clinical testing | The p.V3112F variant (also known as c.9334G>T) is located in coding exon 39 of the TTN gene. The valine at codon 3112 is replaced by phenylalanine, an amino acid with highly similar properties. This change occurs in the first base pair of exon 40 which makes it likely to have some effect on normal mRNA splicing. Based on data from ExAC, the T allele was reported in 1 of 120294 (0.0008%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed February 11, 2016]). This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice acceptor site; however, direct experimental evidence is unavailable. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Ai |
RCV002223882 | SCV002503081 | uncertain significance | not provided | 2021-12-03 | criteria provided, single submitter | clinical testing | |
Gene |
RCV002223882 | SCV003195238 | uncertain significance | not provided | 2022-07-18 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis suggests this variant may impact gene splicing; however, in the absence of RNA/functional studies, the actual effect of this sequence change is unknown; Has not been previously published as pathogenic or benign to our knowledge |