Submissions for variant NM_000492.4(CFTR):c.1538A>G (p.Asp513Gly)

dbSNP: rs397508225

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000577027	SCV000924264	pathogenic	Cystic fibrosis	2017-12-08	reviewed by expert panel	research
CFTR-France	RCV001009541	SCV001169636	pathogenic	Cystic fibrosis; CFTR-related disorder	2018-03-09	criteria provided, single submitter	curation	the variant causes a phenotype but regarding our data, we can't formally attribute it to CF, CFTR-RD or both
Ambry Genetics	RCV000577027	SCV002705849	likely pathogenic	Cystic fibrosis	2015-09-24	criteria provided, single submitter	clinical testing	The p.D513G variant (also known as c.1538A>G and 1670A>G), located in coding exon 11 of the CFTR gene, results from an A to G substitution at nucleotide position 1538. The aspartic acid at codon 513 is replaced by glycine, an amino acid with similar properties. This alteration was first reported in an individual with CBAVD, elevated sweat chloride, pancreatic sufficiency, and normal lung function, who reportedly carried deltaF508 on the other chromosome (Bienvenu T et al. Cystic Fibrosis Mutation Database [database online]. Toronto, ON, Canada: SickKids; 1998). This variant has been detected in conjunction with a pathogenic mutation in CFTR in four patients tested by our laboratory; it was confirmed to be in trans with the pathogenic mutation in one patient. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is highly conserved on sequence alignment. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000577027	SCV003440718	uncertain significance	Cystic fibrosis	2022-04-19	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 513 of the CFTR protein (p.Asp513Gly). This variant is present in population databases (rs397508225, gnomAD 0.0009%). This missense change has been observed in individual(s) with cystic fibrosis (PMID: 10651488, 23974870, 33572515). ClinVar contains an entry for this variant (Variation ID: 53280). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C35"). Experimental studies have shown that this missense change affects CFTR function (PMID: 29805046). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Baylor Genetics	RCV004566863	SCV005057425	likely pathogenic	Bronchiectasis with or without elevated sweat chloride 1	2024-03-04	criteria provided, single submitter	clinical testing
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000577027	SCV000679110	not provided	Cystic fibrosis		no assertion provided	literature only