Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV001004892 | SCV001164386 | uncertain significance | Saldino-Mainzer syndrome | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.His102Tyr variant in IFT140 was identified by our study in one individual in the compound heterozygous state, with another VUS, with Short-Rib Thoracic Dysplasia with or without Polydactyly. The p.His102Tyr variant in IFT140 has not been previously reported in individuals with Short-Rib Thoracic Dysplasia with or without Polydactyly and was absent from large population studies. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, the clinical significance of the p.His102Tyr variant is uncertain. ACMG/AMP Criteria applied: PM2, PP3 (Richards 2015). |
Invitae | RCV001004892 | SCV001208055 | uncertain significance | Saldino-Mainzer syndrome | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 102 of the IFT140 protein (p.His102Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of IFT140-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 813921). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |