Submissions for variant NM_015662.3(IFT172):c.1523G>A (p.Arg508His)

gnomAD frequency: 0.00030  dbSNP: rs144868723

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001053472	SCV001217736	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2022-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 508 of the IFT172 protein (p.Arg508His). This variant is present in population databases (rs144868723, gnomAD 0.1%). 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: 849493). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
New York Genome Center	RCV001053472	SCV002764474	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2021-12-12	criteria provided, single submitter	clinical testing
GeneDx	RCV002553321	SCV003195089	uncertain significance	not provided	2023-01-05	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
Dept Of Ophthalmology, Nagoya University	RCV003890196	SCV004705271	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Breakthrough Genomics, Breakthrough Genomics	RCV002553321	SCV005187514	uncertain significance	not provided		criteria provided, single submitter	not provided
PreventionGenetics, part of Exact Sciences	RCV004553592	SCV004750470	likely benign	IFT172-related disorder	2022-02-03	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).