Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001546027 | SCV001765469 | likely benign | not provided | 2020-03-17 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282561 | SCV002572420 | likely benign | not specified | 2022-08-29 | criteria provided, single submitter | clinical testing | Variant summary: TTN c.94460T>C (p.Val31487Ala) results in a non-conservative amino acid change located in the M-band region of the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 248340 control chromosomes, predominantly at a frequency of 0.00099 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 2.5-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 Latino origin. c.94460T>C has been reported in the literature in an individual affected with polymicrogyria (Allen_2021). This individual also had a de novo co-occurrence classified as pathogenic by the authors (CCND2 p.Thr280Asp). This report does 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. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
Revvity Omics, |
RCV001546027 | SCV003820296 | uncertain significance | not provided | 2022-06-13 | criteria provided, single submitter | clinical testing |