NM_001903.5(CTNNA1):c.2191C>T (p.Arg731Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jan 22, 2025
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:: RCV000816771.9

Allele description [Variation Report for NM_001903.5(CTNNA1):c.2191C>T (p.Arg731Ter)]

NM_001903.5(CTNNA1):c.2191C>T (p.Arg731Ter)

Gene:

CTNNA1:catenin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q31.2

Genomic location:

Preferred name:

NM_001903.5(CTNNA1):c.2191C>T (p.Arg731Ter)

Other names:

p.Arg731

HGVS:

NC_000005.10:g.138930653C>T
NG_047029.1:g.182258C>T
NM_001290307.3:c.2191C>T
NM_001290309.3:c.1882C>T
NM_001290310.3:c.1822C>T
NM_001290312.1:c.1081C>T
NM_001323982.2:c.2191C>T
NM_001323983.1:c.2191C>T
NM_001323984.2:c.2191C>T
NM_001323985.2:c.2191C>T
NM_001323986.2:c.2098C>T
NM_001323987.1:c.1081C>T
NM_001323988.1:c.1081C>T
NM_001323989.1:c.1081C>T
NM_001323990.1:c.1081C>T
NM_001323991.1:c.1081C>T
NM_001323992.1:c.1081C>T
NM_001323993.1:c.1081C>T
NM_001323994.1:c.1081C>T
NM_001323995.1:c.1081C>T
NM_001323996.1:c.1081C>T
NM_001323997.1:c.1081C>T
NM_001323998.1:c.1081C>T
NM_001323999.1:c.1081C>T
NM_001324000.1:c.1081C>T
NM_001324001.1:c.1081C>T
NM_001324002.1:c.1081C>T
NM_001324003.1:c.1081C>T
NM_001324004.1:c.1081C>T
NM_001324005.1:c.1081C>T
NM_001324006.1:c.742C>T
NM_001324007.1:c.742C>T
NM_001324008.1:c.742C>T
NM_001324009.1:c.742C>T
NM_001324010.1:c.742C>T
NM_001324011.1:c.988C>T
NM_001324012.1:c.838C>T
NM_001324013.1:c.838C>T
NM_001903.5:c.2191C>TMANE SELECT
NP_001277236.1:p.Arg731Ter
NP_001277238.1:p.Arg628Ter
NP_001277239.1:p.Arg608Ter
NP_001277241.1:p.Arg361Ter
NP_001310911.1:p.Arg731Ter
NP_001310912.1:p.Arg731Ter
NP_001310913.1:p.Arg731Ter
NP_001310914.1:p.Arg731Ter
NP_001310915.1:p.Arg700Ter
NP_001310916.1:p.Arg361Ter
NP_001310917.1:p.Arg361Ter
NP_001310918.1:p.Arg361Ter
NP_001310919.1:p.Arg361Ter
NP_001310920.1:p.Arg361Ter
NP_001310921.1:p.Arg361Ter
NP_001310922.1:p.Arg361Ter
NP_001310923.1:p.Arg361Ter
NP_001310924.1:p.Arg361Ter
NP_001310925.1:p.Arg361Ter
NP_001310926.1:p.Arg361Ter
NP_001310927.1:p.Arg361Ter
NP_001310928.1:p.Arg361Ter
NP_001310929.1:p.Arg361Ter
NP_001310930.1:p.Arg361Ter
NP_001310931.1:p.Arg361Ter
NP_001310932.1:p.Arg361Ter
NP_001310933.1:p.Arg361Ter
NP_001310934.1:p.Arg361Ter
NP_001310935.1:p.Arg248Ter
NP_001310936.1:p.Arg248Ter
NP_001310937.1:p.Arg248Ter
NP_001310938.1:p.Arg248Ter
NP_001310939.1:p.Arg248Ter
NP_001310940.1:p.Arg330Ter
NP_001310941.1:p.Arg280Ter
NP_001310942.1:p.Arg280Ter
NP_001894.2:p.Arg731Ter
NC_000005.9:g.138266342C>T
NM_001903.2:c.2191C>T
NM_001903.3:c.2191C>T
NM_001903.5:c.2191C>T

Protein change:

R248*

Links:

dbSNP: rs1401839892

NCBI 1000 Genomes Browser:

rs1401839892

Molecular consequence:

NM_001290307.3:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001290309.3:c.1882C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001290310.3:c.1822C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001290312.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323982.2:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323983.1:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323984.2:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323985.2:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323986.2:c.2098C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323987.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323988.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323989.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323990.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323991.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323992.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323993.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323994.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323995.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323996.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323997.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323998.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323999.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324000.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324001.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324002.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324003.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324004.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324005.1:c.1081C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324006.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324007.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324008.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324009.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324010.1:c.742C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324011.1:c.988C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324012.1:c.838C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001324013.1:c.838C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001903.5:c.2191C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000957296	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 22, 2025)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 34425242, 32051609, 28492532
SCV005442980	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Jul 2, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000957296

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 22, 2025)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV005442980

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Jul 2, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Cancer predisposition and germline CTNNA1 variants.

Lobo S, Benusiglio PR, Coulet F, Boussemart L, Golmard L, Spier I, Hüneburg R, Aretz S, Colas C, Oliveira C.

Eur J Med Genet. 2021 Oct;64(10):104316. doi: 10.1016/j.ejmg.2021.104316. Epub 2021 Aug 21.

PubMed [citation]

PMID:: 34425242

Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer.

Clark DF, Michalski ST, Tondon R, Nehoray B, Ebrahimzadeh J, Hughes SK, Soper ER, Domchek SM, Rustgi AK, Pineda-Alvarez D, Anderson MJ, Katona BW.

Genet Med. 2020 May;22(5):840-846. doi: 10.1038/s41436-020-0753-1. Epub 2020 Feb 13.

PubMed [citation]

PMID:: 32051609
PMCID:: PMC7200596

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000957296.7

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

Description

This sequence change creates a premature translational stop signal (p.Arg731*) in the CTNNA1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CTNNA1 are known to be pathogenic (PMID: 32051609, 34425242). 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 a family history of early-onset breast cancer (PMID: 32051609). ClinVar contains an entry for this variant (Variation ID: 659725). For these reasons, this variant has been classified as Pathogenic.

#	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, SCV005442980.1

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

Description

Nonsense 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; Not observed at significant frequency in large population cohorts (gnomAD); Observed in individuals referred for hereditary cancer multi-gene panel testing (PMID: 32051609); This variant is associated with the following publications: (PMID: 34425242, 32051609)

#	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: Apr 13, 2025

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Relating variation to medicine