Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000040760 | SCV000064451 | uncertain significance | not specified | 2012-03-22 | criteria provided, single submitter | clinical testing | The Arg27336His variant (TTN) has not been reported in the literature but has be en identified in one individual with DCM tested by our laboratory. Arginine (Arg ) at position 27336 is conserved in evolutionarily distant species, increasing t he likelihood that a change would not be tolerated. Computational predictions ar e inconsistent (AlignGVGD = benign, SIFT = pathogenic), though their accuracy is unknown. Additional data is required to assess the clinical significance of thi s variant. |
| Invitae | RCV000231353 | SCV000286900 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2017-10-26 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002362638 | SCV002660778 | uncertain significance | Cardiovascular phenotype | 2019-02-14 | criteria provided, single submitter | clinical testing | The p.R20839H variant (also known as c.62516G>A), located in coding exon 162 of the TTN gene, results from a G to A substitution at nucleotide position 62516. The arginine at codon 20839 is replaced by histidine, an amino acid with highly similar properties. 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. |
| Fulgent Genetics, |
RCV002504914 | SCV002814334 | 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 | 2021-07-13 | criteria provided, single submitter | clinical testing | |
| New York Genome Center | RCV003227626 | SCV003925348 | uncertain significance | Dilated cardiomyopathy 1G; Hypertrophic cardiomyopathy 9 | 2022-04-08 | criteria provided, single submitter | clinical testing | The c.89711G>A (p. Arg29904His) missense variant in the TTN gene identified in exon 335 (of 363) of this individual has not been reported in affected individuals in the literature. The variant has 0.00003943 allele frequency in the gnomAD (v3.1.2) database (6 out of 152164 heterozygous alleles, no homozygotes)suggesting it is not a common benign variant in the populations represented in that database. This variant is reported as a variant of uncertain significance in the ClinVar database (Variation ID: 47491). The variant affects a conserved residue (Arg29904) located in the Ig like and fibronectin type III domain of A-Band of TTN protein (PMID: 29238064, Uniprot and http://cardiodb.org/titin/). In silico predictions are moderately in favor of damaging effect for p. Arg29904His (CADD score =34,REVEL score = 0.486). Based on the available evidence, the c.89711G>A (p. Arg29904His) missense variant identified in the TTN gene is reported as a Variant of Uncertain Significance. |