Submissions for variant NM_000492.4(CFTR):c.1505T>C (p.Ile502Thr)

gnomAD frequency: 0.00001  dbSNP: rs397508222

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000577239	SCV000924262	pathogenic	Cystic fibrosis	2018-08-31	reviewed by expert panel	research
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577239	SCV002296421	uncertain significance	Cystic fibrosis	2020-10-30	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 26911355, 15638824). ClinVar contains an entry for this variant (Variation ID: 53272). This variant is present in population databases (rs397508222, ExAC 0.006%). This sequence change replaces isoleucine with threonine at codon 502 of the CFTR protein (p.Ile502Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine.
Johns Hopkins Genomics, Johns Hopkins University	RCV000577239	SCV002570229	pathogenic	Cystic fibrosis	2022-06-15	criteria provided, single submitter	clinical testing	Disease-causing CFTR variant. See www.CFTR2.org for phenotype information.
Ambry Genetics	RCV000577239	SCV002702407	pathogenic	Cystic fibrosis	2016-04-29	criteria provided, single submitter	clinical testing	The p.I502T pathogenic mutation (also known as c.1505T>C and 1637T>C), located in coding exon 11 of the CFTR gene, results from a T to C substitution at nucleotide position 1505. The isoleucine at codon 502 is replaced by threonine, an amino acid with similar properties. This mutation was first detected in 8 alleles of Italian individuals with cystic fibrosis (CF) and elevated sweat chloride levels; however, specific genotype information was not provided (Castaldo G, Ann. Hum. Genet. 2005 Jan; 69(Pt 1):15-24). In addition, elevated sweat chloride levels were observed in six individuals with CF and a known pathogenic mutation on the the other allele (Masica DL, Hum. Mol. Genet. 2015 Apr; 24(7):1908-17). Based on the supporting evidence, p.I502T is interpreted as a disease-causing mutation.
Baylor Genetics	RCV003473457	SCV004213486	pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2023-06-20	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577239	SCV000679327	not provided	Cystic fibrosis		no assertion provided	literature only
Natera, Inc.	RCV000577239	SCV001460189	pathogenic	Cystic fibrosis	2020-09-16	no assertion criteria provided	clinical testing