Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000040612 | SCV000064303 | uncertain significance | not specified | 2012-09-21 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Arg22789His var iant in TTN has not been reported in the literature, but has been identified in 1 child with HCM and RCM tested by our laboratory, who also carried another de n ovo variant sufficient to explain disease. Arginine (Arg) at position 22789 is n ot completely conserved in mammals and several mammals (guinea pig, armadillo, s loth) carry a histidine (His, this variant) despite high nearby amino acid conse rvation, suggesting that this change may be tolerated. Additional computational analyses (biochemical amino acid properties, AlignGVGD, and PolyPhen2) suggest t hat this variant may not impact the protein, though this information is not pred ictive enough to rule out pathogenicity. In summary, the available data suggests that this variant is more likely benign, but additional studies are needed to f ully assess its clinical significance. |
Invitae | RCV000467480 | SCV000543059 | uncertain significance | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2016-12-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000040612 | SCV001360626 | uncertain significance | not specified | 2021-07-19 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.68366G>A (p.Arg22789His) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 248156 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.68366G>A in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported in the literature. One ClinVar submitter (evaluation after 2014) cites the variant as likely benign while another ClinVar submitter (evaluation after 2014) cites it as uncertain significance. A different ClinVar submitter (evaluation before 2014) cited evidence of the variant identified in 1 child with HCM and RCM tested by their laboratory, who also carried another de novo variant sufficient to explain disease (SCV000064303.6). Based on the evidence outlined above, the variant was classified as uncertain significance until additional evidence of clinical and/or functional importance becomes available. |
Gene |
RCV001534450 | SCV001751381 | likely benign | not provided | 2018-09-10 | criteria provided, single submitter | clinical testing |