NM_000492.4(CFTR):c.148T>C (p.Ser50Pro) AND Cystic fibrosis

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 12, 2023
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:: RCV000046319.9

Allele description [Variation Report for NM_000492.4(CFTR):c.148T>C (p.Ser50Pro)]

NM_000492.4(CFTR):c.148T>C (p.Ser50Pro)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

7q31.2

Genomic location:

Preferred name:

NM_000492.4(CFTR):c.148T>C (p.Ser50Pro)

HGVS:

NC_000007.14:g.117504347T>C
NG_016465.4:g.43564T>C
NM_000492.4:c.148T>CMANE SELECT
NP_000483.3:p.Ser50Pro
NP_000483.3:p.Ser50Pro
LRG_663t1:c.148T>C
LRG_663:g.43564T>C
LRG_663p1:p.Ser50Pro
NC_000007.13:g.117144401T>C
NM_000492.3:c.148T>C

Protein change:

S50P

Links:

dbSNP: rs397508217

NCBI 1000 Genomes Browser:

rs397508217

Molecular consequence:

NM_000492.4:c.148T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cystic fibrosis (CF)
Synonyms:: Mucoviscidosis
Identifiers:: MONDO: MONDO:0009061; MedGen: C0010674; Orphanet: 586; OMIM: 219700

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000074332	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 12, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18306312, 10612827, 10875853, 25697318, 28492532
SCV001169474	CFTR-France	criteria provided, single submitter (Claustres M et al. (Hum Mutat 2017))	Pathogenic (Jul 3, 2015)	germline	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000074332

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 12, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV001169474

CFTR-France

criteria provided, single submitter

(Claustres M et al. (Hum Mutat 2017))

Pathogenic
(Jul 3, 2015)

germline

curation

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

N-terminal CFTR missense variants severely affect the behavior of the CFTR chloride channel.

Gené GG, Llobet A, Larriba S, de Semir D, Martínez I, Escalada A, Solsona C, Casals T, Aran JM.

Hum Mutat. 2008 May;29(5):738-49. doi: 10.1002/humu.20721.

PubMed [citation]

PMID:: 18306312

UMD (Universal mutation database): a generic software to build and analyze locus-specific databases.

Béroud C, Collod-Béroud G, Boileau C, Soussi T, Junien C.

Hum Mutat. 2000;15(1):86-94.

PubMed [citation]

PMID:: 10612827

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000074332.8

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CFTR function (PMID: 18306312). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CFTR protein function. ClinVar contains an entry for this variant (Variation ID: 53266). This missense change has been observed in individual(s) with congenital bilateral absence of the vas deferens (CBAVD) and cystic fibrosis (PMID: 10612827, 10875853, 25697318; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 50 of the CFTR protein (p.Ser50Pro).

#	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 CFTR-France, SCV001169474.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	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: Sep 29, 2024

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