Submissions for variant NM_015662.3(IFT172):c.706C>T (p.Arg236Cys)

gnomAD frequency: 0.00015  dbSNP: rs146290725

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001228451	SCV001400851	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2024-02-16	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 236 of the IFT172 protein (p.Arg236Cys). This variant is present in population databases (rs146290725, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with IFT172-related conditions. ClinVar contains an entry for this variant (Variation ID: 955756). 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 expected to disrupt IFT172 protein function with a positive 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	RCV001664769	SCV001873618	uncertain significance	not provided	2021-08-12	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Fulgent Genetics, Fulgent Genetics	RCV002491722	SCV002801537	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71; Bardet-Biedl syndrome 20	2022-04-05	criteria provided, single submitter	clinical testing
Dept Of Ophthalmology, Nagoya University	RCV003887926	SCV004705276	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Ambry Genetics	RCV004986980	SCV005604251	uncertain significance	Inborn genetic diseases	2024-11-13	criteria provided, single submitter	clinical testing	The c.706C>T (p.R236C) alteration is located in exon 8 (coding exon 8) of the IFT172 gene. This alteration results from a C to T substitution at nucleotide position 706, causing the arginine (R) at amino acid position 236 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV004548080	SCV004755879	uncertain significance	IFT172-related disorder	2024-02-09	no assertion criteria provided	clinical testing	The IFT172 c.706C>T variant is predicted to result in the amino acid substitution p.Arg236Cys. This variant has been detected in a cohort of Japanese individuals with retinitis pigmentosa and was considered of uncertain significance (Table S5 Koyanagi et al. 2019. PubMed ID: 31213501). This variant is reported in 0.028% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.