Submissions for variant NM_015662.3(IFT172):c.3435T>G (p.His1145Gln)

gnomAD frequency: 0.00017  dbSNP: rs202111577

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000997101	SCV001152212	uncertain significance	not provided	2016-09-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001044113	SCV001207890	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2024-01-19	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1145 of the IFT172 protein (p.His1145Gln). This variant is present in population databases (rs202111577, gnomAD 0.03%). 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: 808718). 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 not expected to disrupt IFT172 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.
Genetic Services Laboratory, University of Chicago	RCV001819709	SCV002072369	uncertain significance	not specified	2019-03-29	criteria provided, single submitter	clinical testing
Laboratory of Molecular Genetics (Pr. Bezieau's lab), CHU de Nantes	RCV002279692	SCV002564456	uncertain significance	Neurodevelopmental disorder	2021-12-15	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000997101	SCV003813254	uncertain significance	not provided	2021-06-16	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000997101	SCV005187447	uncertain significance	not provided		criteria provided, single submitter	not provided
Fulgent Genetics, Fulgent Genetics	RCV005029552	SCV005656039	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71; Bardet-Biedl syndrome 20	2024-03-22	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004553539	SCV004110585	uncertain significance	IFT172-related disorder	2024-02-14	no assertion criteria provided	clinical testing	The IFT172 c.3435T>G variant is predicted to result in the amino acid substitution p.His1145Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.034% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.