Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Mendelics | RCV000033956 | SCV001141471 | uncertain significance | Orofaciodigital syndrome I | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001852686 | SCV002185721 | uncertain significance | Familial aplasia of the vermis; Orofaciodigital syndrome I | 2023-05-19 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt OFD1 protein function. ClinVar contains an entry for this variant (Variation ID: 41057). This missense change has been observed in individual(s) with oral-facial-digital syndrome and/or retinitis pigmentosa (PMID: 18546297; Invitae). This variant is present in population databases (rs312262864, gnomAD 0.001%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 367 of the OFD1 protein (p.Arg367Gln). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317054 | SCV004020934 | uncertain significance | not specified | 2023-06-22 | criteria provided, single submitter | clinical testing | Variant summary: OFD1 c.1100G>A (p.Arg367Gln) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 5.5e-06 in 183380 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1100G>A has been reported in the literature in at least one individual affected with Orofaciodigital Syndrome I (example: Prattichizzo_2008). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 18546297). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |