Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000729526 | SCV000716053 | likely benign | not provided | 2018-12-05 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 28714951) |
| Eurofins Ntd Llc |
RCV000729526 | SCV000857196 | uncertain significance | not provided | 2017-10-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001087612 | SCV001002206 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-01-20 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002298706 | SCV002598995 | likely benign | not specified | 2022-09-06 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.5255G>A (p.Arg1752His) results in a non-conservative amino acid change located in the near Z disk/I-band region of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 250778 control chromosomes, predominantly at a frequency of 0.0011 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 3 fold of the estimated maximal predicted allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. c.5255G>A has been reported in the literature as a de novo occurrence in at-least one individual affected with autism (example: Lim_2017 and Turner_2019). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as VUS (n=1) and likely benign (n=2). Based on the evidence outlined above, the variant was classified as likely benign. |
| Ambry Genetics | RCV002341551 | SCV002644674 | uncertain significance | Cardiovascular phenotype | 2019-09-23 | criteria provided, single submitter | clinical testing | The p.R1706H variant (also known as c.5117G>A), located in coding exon 26 of the TTN gene, results from a G to A substitution at nucleotide position 5117. The arginine at codon 1706 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. |