ClinVar Genomic variation as it relates to human health
NM_001903.5(CTNNA1):c.2493G>C (p.Gln831His)
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance(3); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001903.5(CTNNA1):c.2493G>C (p.Gln831His)
Variation ID: 643191 Accession: VCV000643191.14
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 5q31.2 5: 138933861 (GRCh38) [ NCBI UCSC ] 5: 138269550 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Aug 14, 2019 May 1, 2024 Jan 31, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_001903.5:c.2493G>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001894.2:p.Gln831His missense NM_001290307.3:c.*38G>C 3 prime UTR NM_001290309.3:c.2184G>C NP_001277238.1:p.Gln728His missense NM_001290310.3:c.2124G>C NP_001277239.1:p.Gln708His missense NM_001290312.1:c.1383G>C NP_001277241.1:p.Gln461His missense NM_001323982.2:c.2493G>C NP_001310911.1:p.Gln831His missense NM_001323983.1:c.2493G>C NP_001310912.1:p.Gln831His missense NM_001323984.2:c.2493G>C NP_001310913.1:p.Gln831His missense NM_001323985.2:c.2466G>C NP_001310914.1:p.Gln822His missense NM_001323986.2:c.2400G>C NP_001310915.1:p.Gln800His missense NM_001323987.1:c.1383G>C NP_001310916.1:p.Gln461His missense NM_001323988.1:c.1383G>C NP_001310917.1:p.Gln461His missense NM_001323989.1:c.1383G>C NP_001310918.1:p.Gln461His missense NM_001323990.1:c.1383G>C NP_001310919.1:p.Gln461His missense NM_001323991.1:c.1383G>C NP_001310920.1:p.Gln461His missense NM_001323992.1:c.1383G>C NP_001310921.1:p.Gln461His missense NM_001323993.1:c.1383G>C NP_001310922.1:p.Gln461His missense NM_001323994.1:c.1383G>C NP_001310923.1:p.Gln461His missense NM_001323995.1:c.1383G>C NP_001310924.1:p.Gln461His missense NM_001323996.1:c.1383G>C NP_001310925.1:p.Gln461His missense NM_001323997.1:c.1383G>C NP_001310926.1:p.Gln461His missense NM_001323998.1:c.1383G>C NP_001310927.1:p.Gln461His missense NM_001323999.1:c.1383G>C NP_001310928.1:p.Gln461His missense NM_001324000.1:c.1383G>C NP_001310929.1:p.Gln461His missense NM_001324001.1:c.1248G>C NP_001310930.1:p.Gln416His missense NM_001324002.1:c.*38G>C 3 prime UTR NM_001324003.1:c.*38G>C 3 prime UTR NM_001324004.1:c.*38G>C 3 prime UTR NM_001324005.1:c.*38G>C 3 prime UTR NM_001324006.1:c.1044G>C NP_001310935.1:p.Gln348His missense NM_001324007.1:c.1044G>C NP_001310936.1:p.Gln348His missense NM_001324008.1:c.1044G>C NP_001310937.1:p.Gln348His missense NM_001324009.1:c.1044G>C NP_001310938.1:p.Gln348His missense NM_001324010.1:c.1044G>C NP_001310939.1:p.Gln348His missense NM_001324011.1:c.1290G>C NP_001310940.1:p.Gln430His missense NM_001324012.1:c.1140G>C NP_001310941.1:p.Gln380His missense NM_001324013.1:c.1140G>C NP_001310942.1:p.Gln380His missense NC_000005.10:g.138933861G>C NC_000005.9:g.138269550G>C NG_047029.1:g.185466G>C - Protein change
- Q461H, Q728H, Q831H, Q348H, Q380H, Q416H, Q822H, Q430H, Q708H, Q800H
- Other names
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- Canonical SPDI
- NC_000005.10:138933860:G:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD) 0.00005
Exome Aggregation Consortium (ExAC) 0.00006
The Genome Aggregation Database (gnomAD), exomes 0.00008
Trans-Omics for Precision Medicine (TOPMed) 0.00008
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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CTNNA1 | Sufficient evidence for dosage pathogenicity | No evidence available |
GRCh38 GRCh37 |
2824 | 2880 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
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The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 31, 2024 | RCV000796840.7 | |
Likely benign (1) |
criteria provided, single submitter
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May 9, 2023 | RCV001015698.4 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 26, 2023 | RCV003472349.1 | |
Likely benign (1) |
criteria provided, single submitter
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Mar 8, 2023 | RCV003316810.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
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This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(Oct 25, 2022)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV003921325.1
First in ClinVar: May 06, 2023 Last updated: May 06, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals referred for hereditary cancer multi-gene panel testing … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals referred for hereditary cancer multi-gene panel testing (Clark et al., 2020); This variant is associated with the following publications: (PMID: 32051609) (less)
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Likely benign
(Mar 08, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary diffuse gastric adenocarcinoma
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV004020166.1
First in ClinVar: Jul 29, 2023 Last updated: Jul 29, 2023 |
Comment:
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease … (more)
This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance. (less)
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Uncertain significance
(Sep 26, 2023)
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criteria provided, single submitter
Method: clinical testing
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Patterned macular dystrophy 2
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004211273.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Uncertain significance
(Jan 31, 2024)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000936369.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 831 of the CTNNA1 protein (p.Gln831His). … (more)
This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 831 of the CTNNA1 protein (p.Gln831His). This variant is present in population databases (rs781450977, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with CTNNA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 643191). 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 not expected to disrupt CTNNA1 protein function with a negative predictive value of 80%. 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. (less)
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Likely benign
(May 09, 2023)
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criteria provided, single submitter
Method: clinical testing
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Hereditary cancer-predisposing syndrome
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV001176560.5
First in ClinVar: Mar 16, 2020 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Loss-of-function variants in CTNNA1 detected on multigene panel testing in individuals with gastric or breast cancer. | Clark DF | Genetics in medicine : official journal of the American College of Medical Genetics | 2020 | PMID: 32051609 |
Text-mined citations for rs781450977 ...
HelpRecord last updated May 01, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.