Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000250569 | SCV000320628 | uncertain significance | Cardiovascular phenotype | 2015-12-14 | criteria provided, single submitter | clinical testing | The p.S19893N variant (also known as c.59678G>A), located in coding exon 154 of the TTN gene, results from a G to A substitution at nucleotide position 59678. The serine at codon 19893 is replaced by asparagine, an amino acid with highly similar properties. This variant was previously reported in the SNPDatabase as rs199639729. Based on data from the NHLBI Exome Sequencing Project (ESP), the A allele has an overall frequency of approximately 0.02% (2/11974) total alleles studied and 0.02% (2/8216) European American alleles. Based on data from ExAC, the A allele was reported in 9 of 119262 (0.008%) total alleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed December 8, 2015]). 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 variant remains unclear. |
| ARUP Laboratories, |
RCV001812762 | SCV001473501 | uncertain significance | not provided | 2020-02-16 | criteria provided, single submitter | clinical testing | The TTN c.86873G>A; p.Ser28958Asn variant (rs199639729; ClinVar Variation ID: 264600) 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.Ser28958Asn 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. |
| Mayo Clinic Laboratories, |
RCV001812762 | SCV004225796 | uncertain significance | not provided | 2022-03-17 | criteria provided, single submitter | clinical testing | PM2 |