Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000403385 | SCV000475603 | uncertain significance | Loeys-Dietz syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000298980 | SCV000475604 | uncertain significance | Loeys-Dietz syndrome 1 | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000356175 | SCV000475605 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589811 | SCV000698482 | uncertain significance | not provided | 2017-06-14 | criteria provided, single submitter | clinical testing | Variant summary: The TGFBR1 c.-13T>C variant involves the alteration of a non-conserved nucleotide in the 5UTR region. One in silico tool predicts a benign outcome for this variant. 4/5 splice prediction tools predict no significant impact on normal splicing. ESE finder predicts that this variant may affect ESE sites. However, these predictions have yet to be confirmed by functional studies. This variant was found in 5/26312 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000372 (5/13448). This frequency is about 198 times the estimated maximal expected allele frequency of a pathogenic TGFBR1 variant (0.0000019), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. However, this genomic site was noted to be in a low-quality site in gnomAD, thus this data needs to be taken with caution. The fact that this variant is residing within the sequence of GGC GGT/C GGC GGC makes it more prone to false postive calls. In addition, one other clinical diagnostic laboratory classified this variant as uncertain significance, without evidence for independent evaluation. The variant of interest has not, to our knowledge, been reported in affected individuals via publications; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as VUS-possibly benign until more evidence becomes available. |
Fulgent Genetics, |
RCV002481248 | SCV002782406 | uncertain significance | Loeys-Dietz syndrome 1; Multiple self-healing squamous epithelioma | 2021-10-19 | criteria provided, single submitter | clinical testing |