ClinVar Miner

Submissions for variant NM_003611.3(OFD1):c.149A>G (p.His50Arg)

gnomAD frequency: 0.00001  dbSNP: rs863225213
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
UW Hindbrain Malformation Research Program, University of Washington RCV000201618 SCV000256458 pathogenic Joubert syndrome 10 2015-02-23 criteria provided, single submitter research
Labcorp Genetics (formerly Invitae), Labcorp RCV001307208 SCV001496610 uncertain significance Familial aplasia of the vermis; Orofaciodigital syndrome I 2024-12-27 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 50 of the OFD1 protein (p.His50Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Joubert syndrome (PMID: 26092869). ClinVar contains an entry for this variant (Variation ID: 217687). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt OFD1 protein function with a negative predictive value of 80%. 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.
GeneDx RCV002307444 SCV002601203 uncertain significance not provided 2022-11-08 criteria provided, single submitter clinical testing Identified in a patient with Joubert syndrome in published literature (Bachmann-Gagescu et al., 2015; Vilboux et al., 2017; Pezzella et al., 2022); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 28125082, 35112477, 26092869)
Mayo Clinic Laboratories, Mayo Clinic RCV002307444 SCV005411411 uncertain significance not provided 2023-07-12 criteria provided, single submitter clinical testing PM2_moderate

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