Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Institute of Human Genetics, |
RCV001785239 | SCV002026147 | pathogenic | Saldino-Mainzer syndrome | 2021-10-07 | criteria provided, single submitter | clinical testing | _x000D_ Criteria applied: PVS1, PM2_SUP_MOD, PM3 |
| Labcorp Genetics |
RCV001785239 | SCV002177947 | pathogenic | Saldino-Mainzer syndrome | 2021-06-01 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with retinal dystrophy (PMID: 31630094). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1031841). This sequence change creates a premature translational stop signal (p.Arg347*) in the IFT140 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IFT140 are known to be pathogenic (PMID: 22503633, 23418020, 24009529, 26216056). This variant is not present in population databases (ExAC no frequency). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic. |
| Fulgent Genetics, |
RCV002503275 | SCV002810530 | pathogenic | Saldino-Mainzer syndrome; Retinitis pigmentosa 80 | 2024-06-17 | criteria provided, single submitter | clinical testing | |
| Eurofins- |
RCV001785239 | SCV003935031 | pathogenic | Saldino-Mainzer syndrome | 2022-09-23 | criteria provided, single submitter | clinical testing | |
| Institute of Human Genetics, |
RCV004815633 | SCV005069819 | pathogenic | Retinal dystrophy | 2019-01-01 | criteria provided, single submitter | clinical testing | |
| Victorian Clinical Genetics Services, |
RCV004785311 | SCV005399593 | pathogenic | Renal cyst | 2024-10-10 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with retinitis pigmentosa 80 (MIM#617781), short-rib thoracic dysplasia 9 with or without polydactyly (MIM#266920) and cystic kidney disease (MONDO:0002473), IFT140-related (PMID: 34890546). (I) 0108 - This gene is associated with both recessive and dominant disease. Retinitis pigmentosa 80 (MIM#617781) and short-rib thoracic dysplasia 9 with or without polydactyly (MIM#266920) are inherited in an autosomal recessive manner, while cystic kidney disease (MONDO:0002473), IFT140-related is inherited in an autosomal dominant manner (OMIM, PMID: 34890546). (I) 0112 - The dominant condition associated with this gene may have incomplete penetrance. Parents of children with short-rib thoracic dysplasia 9 with or without polydactyly, who carry a single pathogenic variant that has also previously been associated with the dominant cystic kidney disease phenotype, have been reported as unaffected (PMID: 34890546). However, these parents weren't specifically assessed for cystic kidney disease. (I) 0201 - Variant is predicted to cause nonsense-mediated decay (NMD) and loss of protein (premature termination codon is located at least 54 nucleotides upstream of the final exon-exon junction). (SP) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2: 1 heterozygote, 0 homozygotes). (SP) 0701 - Other NMD-predicted variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (DECIPHER). These variants have been reported in families with later onset autosomal dominant polycystic kidney disease (PMID: 34890546) and autosomal recessive IFT140-related conditions (PMIDs: 22503633, 26968735). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. It has been classified as pathogenic by multiple clinical laboratories in ClinVar. This variant has been reported in an individual with autosomal dominant cystic kidney disease and has also been reported, along with a second variant in IFT140, in an individual with early onset retinal dystrophy (PMIDs: 34890546, 31630094). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |