Submissions for variant NM_000492.4(CFTR):c.313del (p.Ile105fs)

dbSNP: rs121908801

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046792	SCV000245889	pathogenic	Cystic fibrosis	2017-03-17	reviewed by expert panel	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759763	SCV000889308	pathogenic	not provided	2017-10-12	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001004425	SCV001163469	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
Myriad Genetics, Inc.	RCV000046792	SCV001193909	pathogenic	Cystic fibrosis	2019-11-12	criteria provided, single submitter	clinical testing	NM_000492.3(CFTR):c.313delA(I105Sfs*2, aka 444delA) is classified as pathogenic in the context of cystic fibrosis. Sources cited for classification include the following: PMID 15176679, 1710600, 9150159 and 9003508. Classification of NM_000492.3(CFTR):c.313delA(I105Sfs*2, aka 444delA) is based on the following criteria: The variant causes a premature termination codon that is expected to be targeted by nonsense-mediated mRNA decay and is reported in individuals with the relevant phenotype. Please note: this variant was assessed in the context of healthy population screening.‚Äã
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046792	SCV001339216	pathogenic	Cystic fibrosis	2020-03-08	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.313delA (p.Ile105SerfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251136 control chromosomes (gnomAD). c.313delA has been reported in the literature, in compound heterozygous or homozygous state, in multiple individuals affected with Cystic Fibrosis (e.g. Behar_2017, Decaestecker_2004, Siryani_2015). These data indicate that the variant is very likely to be associated with disease. Three ClinVar submitters including an expert panel (CFTR2) (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000046792	SCV001580421	pathogenic	Cystic fibrosis	2023-09-10	criteria provided, single submitter	clinical testing	This variant is also known as 444delA. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 48684). This premature translational stop signal has been observed in individual(s) with clinical features of cystic fibrosis (PMID: 1710600, 26208274, 28546993). This variant is present in population databases (rs779091180, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ile105Serfs*2) in the CFTR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFTR are known to be pathogenic (PMID: 1695717, 7691345, 9725922).
Johns Hopkins Genomics, Johns Hopkins University	RCV000046792	SCV003839135	pathogenic	Cystic fibrosis	2022-11-23	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000759763	SCV004226567	pathogenic	not provided	2024-08-05	criteria provided, single submitter	clinical testing	PP5, PM2, PM3, PVS1
Natera, Inc.	RCV001027892	SCV001190614	pathogenic	CFTR-related disorder	2019-05-20	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000759763	SCV001742759	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000759763	SCV001954659	pathogenic	not provided		no assertion criteria provided	clinical testing