Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Laboratory for Molecular Medicine, |
RCV000037153 | SCV000060810 | uncertain significance | not specified | 2012-06-06 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The Ala92Thr varian t in CTF1 has not been reported in the literature nor previously identified by o ur laboratory. This variant has been listed in dbSNP (rs2234933) without frequen cy information. Computational analyses (biochemical amino acid properties, conse rvation, AlignGVGD, PolyPhen2, and SIFT) suggest that this variant may not impac t the protein, though this information is not predictive enough to rule out path ogenicity. Additional information is needed to fully assess the clinical signifi cance of this variant. |
| Blueprint Genetics | RCV000157154 | SCV000206877 | uncertain significance | Primary familial hypertrophic cardiomyopathy | 2015-03-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000557357 | SCV000659704 | benign | Dilated Cardiomyopathy, Dominant | 2025-02-02 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000037153 | SCV002555921 | benign | not specified | 2022-06-16 | criteria provided, single submitter | clinical testing | Variant summary: CTF1 c.274G>A (p.Ala92Thr) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00059 in 147944 control chromosomes in the gnomAD v3.1.2 database, including 1 homozygote. The observed variant frequency is approximately 38-fold of the estimated maximal expected allele frequency for a pathogenic variant in CTF1 causing Dilated Cardiomyopathy phenotype (1.6e-05), strongly suggesting that the variant is benign. c.274G>A has been reported in the literature in individuals affected with Dilated Cardiomyopathy (Erdmann_2000, Akinrinade_2015). 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. A ClinVar submitter (evaluation after 2014) cites the variant as uncertain significance, while another ClinVar submitter (evaluation after 2014) cites it as benign. Based on the evidence outlined above, the variant was classified as benign. |