NM_000492.4(CFTR):c.262_263del (p.Leu88fs) AND not provided

Germline classification:: Pathogenic (10 submissions)
Last evaluated:: Mar 12, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001269534.27

Allele description [Variation Report for NM_000492.4(CFTR):c.262_263del (p.Leu88fs)]

NM_000492.4(CFTR):c.262_263del (p.Leu88fs)

Gene:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.262_263del (p.Leu88fs)

Other names:

394delTT

HGVS:

NC_000007.13:g.117149182_117149183del
NC_000007.14:g.117509131_117509132del
NG_016465.4:g.48348_48349del
NG_062452.1:g.769_770del
NM_000492.4:c.262_263delMANE SELECT
NP_000483.3:p.Leu88fs
NP_000483.3:p.Leu88fs
LRG_663t1:c.262_263del
LRG_663:g.48348_48349del
LRG_663p1:p.Leu88fs
NC_000007.13:g.117149182_117149183del
NC_000007.13:g.117149185_117149186del
NC_000007.13:g.117149185_117149186delTT
NM_000492.3:c.262_263del
NM_000492.3:c.262_263delTT
p.Leu88IlefsX22
p.Leu88fs

Protein change:

L88fs

Links:

OMIM: 602421.0128; dbSNP: rs121908769

NCBI 1000 Genomes Browser:

rs121908769

Molecular consequence:

NM_000492.4:c.262_263del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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secreted frizzled-related protein 1 [Lemur catta]
secreted frizzled-related protein 1 [Lemur catta]
gi|2168882928|ref|XP_045391718.1|

Protein
PREDICTED: protein O-glucosyltransferase 1 [Lipotes vexillifer]
PREDICTED: protein O-glucosyltransferase 1 [Lipotes vexillifer]
gi|602727495|ref|XP_007449194.1|

Protein
transcription initiation factor TFIID subunit 7-like isoform X2 [Homo sapiens]
transcription initiation factor TFIID subunit 7-like isoform X2 [Homo sapiens]
gi|2462629873|ref|XP_054183240.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001449586	Clinical Genetics and Genomics, Karolinska University Hospital	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jan 22, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001470297	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Jan 15, 2020)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 7509310, 16051530, 26467025
SCV001714828	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 20, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001744223	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001955819	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV001963652	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Pathogenic	germline	clinical testing
SCV003820750	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 24, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003923845	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 14, 2023)	germline	clinical testing	Citation Link,
SCV004185484	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Nov 1, 2023)	germline	clinical testing	Citation Link,
SCV005197709	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 12, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

394delTT: a Nordic cystic fibrosis mutation.

Schwartz M, Anvret M, Claustres M, Eiken HG, Eiklid K, Schaedel C, Stolpe L, Tranebjaerg L.

Hum Genet. 1994 Feb;93(2):157-61.

PubMed [citation]

PMID:: 7509310

Spectrum of mutations in CFTR in Finland: 18 years follow-up study and identification of two novel mutations.

Kinnunen S, Bonache S, Casals T, Monto S, Savilahti E, Kere J, Järvelä I.

J Cyst Fibros. 2005 Dec;4(4):233-7. Epub 2005 Jul 26.

PubMed [citation]

PMID:: 16051530

See all PubMed Citations (4)

Details of each submission

From Clinical Genetics and Genomics, Karolinska University Hospital, SCV001449586.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		2	not provided	not provided	not provided

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV001470297.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Mayo Clinic Laboratories, Mayo Clinic, SCV001714828.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen - VKGL Data-share Consensus, SCV001744223.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001955819.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001963652.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Revvity Omics, Revvity, SCV003820750.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV003923845.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Observed multiple times with a pathogenic variant in unrelated patients with cystic fibrosis or a CFTR-related disorder in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes in some cases (PMID: 7509311, 22678879, 28603918, 23974870); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Also known as 394delTT; This variant is associated with the following publications: (PMID: 14872121, 34996830, 31036917, 22975760, 22658665, 7691344, 752596, 9259197, 22678879, 26087176, 16051530, 18456578, 29261177, 32429104, 31589614, 34782259, 23974870, 7509311, 28603918)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004185484.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

Description

CFTR: PM3:Very Strong, PVS1, PM2

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005197709.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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