NM_000492.4(CFTR):c.1523T>G (p.Phe508Cys) AND not specified

Germline classification:: Conflicting classifications of pathogenicity (4 submissions)
Last evaluated:: May 4, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000078978.29

Allele description [Variation Report for NM_000492.4(CFTR):c.1523T>G (p.Phe508Cys)]

NM_000492.4(CFTR):c.1523T>G (p.Phe508Cys)

Genes:

CFTR:CF transmembrane conductance regulator [Gene - OMIM - HGNC]
CFTR-AS1:CFTR antisense RNA 1 [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.1523T>G (p.Phe508Cys)

HGVS:

NC_000007.14:g.117559594T>G
NG_016465.4:g.98811T>G
NM_000492.4:c.1523T>GMANE SELECT
NP_000483.3:p.Phe508Cys
NP_000483.3:p.Phe508Cys
LRG_663t1:c.1523T>G
LRG_663:g.98811T>G
LRG_663p1:p.Phe508Cys
NC_000007.13:g.117199648T>G
NM_000492.3:c.1523T>G
P13569:p.Phe508Cys

Protein change:

F508C; PHE508CYS

Links:

Genetic Testing Registry (GTR): GTR000074114; Genetic Testing Registry (GTR): GTR000500233; UniProtKB: P13569#VAR_000172; OMIM: 602421.0025; dbSNP: rs74571530

NCBI 1000 Genomes Browser:

rs74571530

Molecular consequence:

NM_000492.4:c.1523T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000110845	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Apr 14, 2016)	germline	clinical testing	Citation Link,
SCV000304473	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000538672	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Apr 25, 2016)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002518210	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2019)	Benign (May 4, 2022)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	9	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Eurofins Ntd Llc (ga), SCV000110845.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	9	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	unknown	not provided	not provided	not provided		9	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000304473.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000538672.1

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

Description

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Benign by Emory. Compund heterozygotes foe this variant and %508del variant were clinically normal, therefore this variant has been classified as benign by Kobayashi et al 1990. Frequency of the variant was higher in individuals with CBAVD (Havasi 2008). Phenotype does not meet reporting criteria.

#	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 Mendelics, SCV002518210.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jan 19, 2025

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