ClinVar Miner

Submissions for variant NM_003611.3(OFD1):c.679A>G (p.Ile227Val)

gnomAD frequency: 0.00008  dbSNP: rs748477774
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001213307 SCV001384933 uncertain significance Familial aplasia of the vermis; Orofaciodigital syndrome I 2024-08-21 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 227 of the OFD1 protein (p.Ile227Val). This variant is present in population databases (rs748477774, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of primary ciliary dyskinesia (internal data). ClinVar contains an entry for this variant (Variation ID: 943172). 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 RCV001751392 SCV001988183 uncertain significance not provided 2019-10-08 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis, which includes splice predictors and evolutionary conservation, suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
Ambry Genetics RCV004033886 SCV002662525 uncertain significance Primary ciliary dyskinesia 2020-01-09 criteria provided, single submitter clinical testing The p.I227V variant (also known as c.679A>G), located in coding exon 8 of the OFD1 gene, results from an A to G substitution at nucleotide position 679. The isoleucine at codon 227 is replaced by valine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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