Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV001704959 | SCV000238365 | likely benign | not provided | 2021-05-03 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge |
| Labcorp Genetics |
RCV000545269 | SCV000642877 | likely benign | Dilated cardiomyopathy 1G; Autosomal recessive limb-girdle muscular dystrophy type 2J | 2024-12-22 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001778776 | SCV002014966 | likely benign | not specified | 2021-10-18 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.21905A>G (p.Gln7302Arg) results in a conservative amino acid change located in the I-band region of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00014 in 247040 control chromosomes, predominantly at a frequency of 0.0019 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 5-fold of the estimated maximal expected 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 East Asian origin. c.21905A>G has been reported in the literature in the index individual of a family affected with cardiac conduction disease. A different variant in LMNA gene (c.686T>C, I229T) was shown to co-segregate with disease in affected family members (Gao_2020). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. A co-occurrence with a pathogenic variant has been reported (MYBPC3 c.3624delC, p.Lys1209SerfsX28; Internal testing), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Revvity Omics, |
RCV001704959 | SCV003827416 | uncertain significance | not provided | 2019-08-17 | criteria provided, single submitter | clinical testing |