Submissions for variant NM_015662.3(IFT172):c.3523G>A (p.Val1175Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002637231	SCV003513137	uncertain significance	Short-rib thoracic dysplasia 10 with or without polydactyly; Retinitis pigmentosa 71	2023-11-20	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1175 of the IFT172 protein (p.Val1175Ile). This variant is present in population databases (rs780334650, gnomAD 0.0009%). 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: 2194609). 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.
PreventionGenetics, part of Exact Sciences	RCV004550441	SCV004799276	uncertain significance	IFT172-related disorder	2024-02-09	no assertion criteria provided	clinical testing	The IFT172 c.3523G>A variant is predicted to result in the amino acid substitution p.Val1175Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% 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.