Submissions for variant NM_003611.3(OFD1):c.1412G>C (p.Arg471Pro)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002607181	SCV003506929	uncertain significance	Familial aplasia of the vermis; Orofaciodigital syndrome I	2024-09-11	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 471 of the OFD1 protein (p.Arg471Pro). This variant is present in population databases (rs750027230, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with OFD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2189202). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
PreventionGenetics, part of Exact Sciences	RCV004538824	SCV004104163	uncertain significance	OFD1-related disorder	2022-11-23	criteria provided, single submitter	clinical testing	The OFD1 c.1412G>C variant is predicted to result in the amino acid substitution p.Arg471Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.010% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/X-13775779-G-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.