Submissions for variant NM_000492.4(CFTR):c.443T>C (p.Ile148Thr)

gnomAD frequency: 0.00083  dbSNP: rs35516286

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000047138	SCV000075151	benign	Cystic fibrosis	2024-01-30	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000079009	SCV000110878	benign	not specified	2012-08-06	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000079009	SCV000304500	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001095251	SCV000466503	uncertain significance	CFTR-related disorder	2018-03-06	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001705619	SCV000603005	benign	not provided	2023-11-15	criteria provided, single submitter	clinical testing
Counsyl	RCV000047138	SCV000790922	likely benign	Cystic fibrosis	2017-04-14	criteria provided, single submitter	clinical testing
SIB Swiss Institute of Bioinformatics	RCV000047138	SCV000803630	likely benign	Cystic fibrosis	2024-04-30	criteria provided, single submitter	curation	This variant is interpreted as a likely benign, for Cystic fibrosis, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. BP2 => Observed in trans with a pathogenic variant for a fully penetrant dominant gene/disorder or observed in cis with a pathogenic variant in any inheritance pattern (PMID:12394343).
Mendelics	RCV000047138	SCV000886144	benign	Cystic fibrosis	2023-08-22	criteria provided, single submitter	clinical testing
CFTR-France	RCV000047138	SCV001169190	benign	Cystic fibrosis	2018-01-29	criteria provided, single submitter	curation	the variant does not result in CFTR-RD neither
Ambry Genetics	RCV000047138	SCV001184227	benign	Cystic fibrosis	2015-03-13	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Johns Hopkins Genomics, Johns Hopkins University	RCV000047138	SCV001425332	benign	Cystic fibrosis	2019-06-25	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000079009	SCV001469505	benign	not specified	2019-12-24	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000047138	SCV001737321	likely benign	Cystic fibrosis	2021-06-10	criteria provided, single submitter	clinical testing
GeneDx	RCV001705619	SCV001830562	likely benign	not provided	2021-02-23	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 1284534, 23974870, 9305991, 12394343, 10653141, 11484207, 22658665, 22975760, 20021716, 15287992, 26990548, 7517268, 15017334, 18456578, 18685558, 16822950, 11242048, 19491324, 15371902)
Institute of Human Genetics, University of Leipzig Medical Center	RCV000047138	SCV002574072	uncertain significance	Cystic fibrosis	2022-09-05	criteria provided, single submitter	curation	This variant was identified in 2 unrelated patients with a clinically confirmed diagnosis of cystic fibrosis. The variant was classified in the context of a project re-classifying variants in the German Cystic Fibrosis Registry (Muko.e.V.). Link: https://www.muko.info/angebote/qualitaetsmanagement/register/cf-einrichtungen/mukoweb. Criteria applied: PM5, PP4, BS2, BS3, BP2
CeGaT Center for Human Genetics Tuebingen	RCV001705619	SCV004158944	likely benign	not provided	2023-10-01	criteria provided, single submitter	clinical testing	CFTR: PM5, BS2
Natera, Inc.	RCV000047138	SCV001453949	benign	Cystic fibrosis	2019-08-06	no assertion criteria provided	clinical testing