ClinVar Miner

Submissions for variant NM_014714.4(IFT140):c.2611C>T (p.Arg871Cys)

gnomAD frequency: 0.00003  dbSNP: rs767213195
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV001268630 SCV001447699 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Invitae RCV001380589 SCV001578702 pathogenic Saldino-Mainzer syndrome 2023-07-19 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IFT140 protein function. ClinVar contains an entry for this variant (Variation ID: 987304). This missense change has been observed in individual(s) with clinical features of retinitis pigmentosa (PMID: 26216056, 28559085; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 871 of the IFT140 protein (p.Arg871Cys).
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001724283 SCV001950286 uncertain significance Retinitis pigmentosa 2021-04-01 criteria provided, single submitter curation The p.Arg871Cys variant in IFT140 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3-P. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.
GeneDx RCV001268630 SCV002526224 likely pathogenic not provided 2022-06-13 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31630094, 28559085, 26216056)
MGZ Medical Genetics Center RCV002290678 SCV002579318 uncertain significance Retinitis pigmentosa 80 2021-09-14 criteria provided, single submitter clinical testing

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