Submissions for variant NM_000492.4(CFTR):c.1373del (p.Gly458fs)

dbSNP: rs397508196

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CFTR2	RCV000046285	SCV000924259	pathogenic	Cystic fibrosis	2017-12-08	reviewed by expert panel	research
Counsyl	RCV000046285	SCV000486665	likely pathogenic	Cystic fibrosis	2016-07-19	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001004448	SCV001163493	pathogenic	Cystic fibrosis; Congenital bilateral aplasia of vas deferens from CFTR mutation		criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000046285	SCV001362618	pathogenic	Cystic fibrosis	2023-06-14	criteria provided, single submitter	clinical testing	Variant summary: CFTR c.1373delG (p.Gly458AspfsX11) results in a premature termination codon, predicted to cause an absence of the protein due to nonsense mediated decay, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4.1e-06 in 244091 control chromosomes, predominantly at a frequency of 6.5e-05 within the African or African-American subpopulation in the gnomAD database. c.1373delG has been reported in the literature in an African American individual affected with Cystic Fibrosis (example, Macek_1997). The following publications have been ascertained in the context of this evaluation (PMID: 9150159, 16049310). Multiple clinical diagnostic laboratories and the CFTR2 database have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Invitae	RCV000046285	SCV003002569	pathogenic	Cystic fibrosis	2022-04-28	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gly458Aspfs*11) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with cystic fibrosis (PMID: 9150159). This variant is also known as 1504delG. ClinVar contains an entry for this variant (Variation ID: 53237). For these reasons, this variant has been classified as Pathogenic.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000046285	SCV000692321	pathogenic	Cystic fibrosis	2015-10-28	no assertion criteria provided	clinical testing