Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000245622 | SCV000320627 | uncertain significance | Cardiovascular phenotype | 2015-12-14 | criteria provided, single submitter | clinical testing | The p.R12907H variant (also known as c.38720G>A), located in coding exon 141 of the TTN gene, results from a G to A substitution at nucleotide position 38720. The arginine at codon 12907 is replaced by histidine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs200217934. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/11944) total alleles studied and 0.02% (2/8216) European American alleles. Based on data from ExAC, the A allele was reported in 11 of 119438 (0.009%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed December 7, 2015]). This amino acid position is well conserved in available vertebrate species; however, histidine is the reference amino acid in one 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 variant remains unclear. |
Eurofins Ntd Llc |
RCV000595770 | SCV000701414 | uncertain significance | not provided | 2017-03-07 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000643862 | SCV000765549 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-08-24 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000595770 | SCV001473500 | uncertain significance | not provided | 2020-02-16 | criteria provided, single submitter | clinical testing | The TTN c.65915G>A; p.Arg21972His variant (rs200217934; ClinVar Variation ID: 264599) is rare in the general population (<1% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Arg21972His variant cannot be determined with certainty. References: Begay RL et al. Role of Titin Missense Variants in Dilated Cardiomyopathy. J Am Heart Assoc. 2015 Nov 13;4(11). Herman DS et al. Truncations of titin causing dilated cardiomyopathy. N Engl J Med. 2012 Feb 16;366(7):619-28. |
Revvity Omics, |
RCV000595770 | SCV003826673 | uncertain significance | not provided | 2023-10-17 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000595770 | SCV004225830 | uncertain significance | not provided | 2022-03-17 | criteria provided, single submitter | clinical testing | BP4, PM2 |