Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000487511 | SCV000575025 | likely pathogenic | not provided | 2017-01-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001584198 | SCV001821384 | uncertain significance | not specified | 2021-08-24 | criteria provided, single submitter | clinical testing | Variant summary: IFT140 c.472C>T (p.Arg158Trp) results in a non-conservative amino acid change located in the WD40/YVTN repeat-like containing superfamily domain (IPR015943) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251318 control chromosomes. c.472C>T has been reported in the literature as a compound heterozygous genotype, in at-least three individuals from comprehensively genotyped cohorts (i.e., WES/comprehensive panel based targeted NGS analysis) affected with Retinal dystrophies and/or inherited retinal disease (IRD) (example, Weisschuh_2016 and Weisschuh_2020). These data indicate that the variant may be associated with disease. 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 pathogenic presumably utilizing at-least one citation included in the context of this evaluation (Weisschuh_2016). Based on the evidence outlined above, until additional clinically diagnosed patients supported by conclusive functional evidence is identified, the variant was classified as VUS-possibly pathogenic. |
| Labcorp Genetics |
RCV001856885 | SCV002205883 | uncertain significance | Saldino-Mainzer syndrome | 2022-08-22 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The tryptophan amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 425084). This missense change has been observed in individuals with retinitis pigmentosa (PMID: 26766544, 32531858). This variant is present in population databases (rs755315693, gnomAD 0.009%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 158 of the IFT140 protein (p.Arg158Trp). |
| Fulgent Genetics, |
RCV005018818 | SCV005645304 | likely pathogenic | Saldino-Mainzer syndrome; Retinitis pigmentosa 80 | 2024-01-02 | criteria provided, single submitter | clinical testing |