Submissions for variant NM_014714.4(IFT140):c.2935G>A (p.Glu979Lys)

gnomAD frequency: 0.00014  dbSNP: rs146277966

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000395263	SCV000395125	uncertain significance	Saldino-Mainzer syndrome	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000395263	SCV001206765	uncertain significance	Saldino-Mainzer syndrome	2025-01-06	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 979 of the IFT140 protein (p.Glu979Lys). This variant is present in population databases (rs146277966, gnomAD 0.04%). This variant has not been reported in the literature in individuals affected with IFT140-related conditions. ClinVar contains an entry for this variant (Variation ID: 318040). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt IFT140 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.
Dept Of Ophthalmology, Nagoya University	RCV003888741	SCV004704972	uncertain significance	Retinal dystrophy	2023-10-01	criteria provided, single submitter	research
Fulgent Genetics, Fulgent Genetics	RCV005016697	SCV005642761	likely benign	Saldino-Mainzer syndrome; Retinitis pigmentosa 80	2024-03-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004752851	SCV005366685	uncertain significance	IFT140-related disorder	2024-08-21	no assertion criteria provided	clinical testing	The IFT140 c.2935G>A variant is predicted to result in the amino acid substitution p.Glu979Lys. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.040% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.