Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001069954 | SCV001235154 | likely pathogenic | Saldino-Mainzer syndrome | 2022-11-14 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 863072). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant has been observed in individual(s) with IFT140-related conditions (PMID: 31213501, 34890546). This variant is present in population databases (rs769075694, gnomAD 0.03%). This variant results in the deletion of part of exon 21 (c.2767_2768+2del) of the IFT140 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in IFT140 are known to be pathogenic (PMID: 22503633, 23418020, 24009529, 26216056). |
| Blueprint Genetics | RCV001075635 | SCV001241262 | likely pathogenic | Retinal dystrophy | 2019-02-22 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002282453 | SCV002570861 | likely pathogenic | Retinitis pigmentosa | 2022-07-08 | criteria provided, single submitter | clinical testing | Variant summary: IFT140 c.2767_2768+2delTAGT is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. Three predict the variant creates a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.4e-05 in 148386 control chromosomes (gnomAD). c.2767_2768+2delTAGT has been reported in the literature in at-least one individual genetically diagnosed with Retinitis Pigmentosa along with another variant : USH2A c.2802T>G (Koyanagi_2019). Multiple individuals heterozygous for this variant have also been reported with autosomal dominant polycystic kidney disease (example: Senum_2022) These reports do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Dept Of Ophthalmology, |
RCV001075635 | SCV004704980 | uncertain significance | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research |