NM_000492.4(CFTR):c.244A>G (p.Met82Val) AND Cystic fibrosis

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Feb 24, 2022
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:: RCV000673216.9

Allele description [Variation Report for NM_000492.4(CFTR):c.244A>G (p.Met82Val)]

NM_000492.4(CFTR):c.244A>G (p.Met82Val)

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.244A>G (p.Met82Val)

HGVS:

NC_000007.14:g.117509113A>G
NG_016465.4:g.48330A>G
NG_062452.1:g.751A>G
NM_000492.4:c.244A>GMANE SELECT
NP_000483.3:p.Met82Val
NP_000483.3:p.Met82Val
LRG_663t1:c.244A>G
LRG_663:g.48330A>G
LRG_663p1:p.Met82Val
NC_000007.13:g.117149167A>G
NM_000492.3:c.244A>G
NM_000492.4:c.244A>G

Protein change:

M82V

Links:

dbSNP: rs1554376431

NCBI 1000 Genomes Browser:

rs1554376431

Molecular consequence:

NM_000492.4:c.244A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

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

Recent activity

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receptor-type tyrosine-protein phosphatase S isoform X20 [Homo sapiens]
receptor-type tyrosine-protein phosphatase S isoform X20 [Homo sapiens]
gi|2462566651|ref|XP_054177602.1|

Protein
transcriptional repressor p66-alpha isoform X6 [Cavia porcellus]
transcriptional repressor p66-alpha isoform X6 [Cavia porcellus]
gi|2687709186|ref|XP_063084117.1|

Protein
HTUR_RS02860 [Haloterrigena turkmenica DSM 5511]
HTUR_RS02860 [Haloterrigena turkmenica DSM 5511]
Gene ID:8741152

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000798394	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Uncertain significance (Mar 8, 2018)	unknown	clinical testing	Citation Link,
SCV001412171	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19910674, 28492532
SCV002027335	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 5, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000798394

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Uncertain significance
(Mar 8, 2018)

unknown

clinical testing

Citation Link,

SCV001412171

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV002027335

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Sep 5, 2021)

germline

clinical testing

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	no	not provided	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

Deletion of CFTR translation start site reveals functional isoforms of the protein in CF patients.

Ramalho AS, Lewandowska MA, Farinha CM, Mendes F, Gonçalves J, Barreto C, Harris A, Amaral MD.

Cell Physiol Biochem. 2009;24(5-6):335-46. doi: 10.1159/000257426. Epub 2009 Nov 4.

PubMed [citation]

PMID:: 19910674
PMCID:: PMC2793277

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000798394.1

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001412171.3

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

Description

This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 82 of the CFTR protein (p.Met82Val). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CFTR-related conditions. ClinVar contains an entry for this variant (Variation ID: 557120). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Experimental studies have shown that this missense change does not substantially affect CFTR function (PMID: 19910674). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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 Genome-Nilou Lab, SCV002027335.1

#	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	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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