Submissions for variant NM_020800.3(IFT80):c.869A>G (p.Asn290Ser)

gnomAD frequency: 0.00014  dbSNP: rs138081429

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000184040	SCV001306364	uncertain significance	Asphyxiating thoracic dystrophy 2	2018-01-13	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.
Invitae	RCV001211297	SCV001382828	uncertain significance	Jeune thoracic dystrophy	2023-12-11	criteria provided, single submitter	clinical testing	This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 290 of the IFT80 protein (p.Asn290Ser). This variant is present in population databases (rs138081429, gnomAD 0.2%). This variant has not been reported in the literature in individuals affected with IFT80-related conditions. ClinVar contains an entry for this variant (Variation ID: 202194). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on IFT80 protein function. 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	RCV001753584	SCV001986622	uncertain significance	not provided	2018-09-10	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31589614)
Mendelics	RCV000184040	SCV000236571	likely pathogenic	Asphyxiating thoracic dystrophy 2	2013-12-13	no assertion criteria provided	clinical testing