VCV000230663.7 - ClinVar

NM_005359.6(SMAD4):c.931C>T (p.Gln311Ter)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Pathogenic

This classification is based on the single submission received

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.

Somatic

No data submitted for somatic clinical impact

Somatic

Oncogenicity

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Likely oncogenic

This classification is based on the single submission received

The aggregate oncogenicity classification for this variant for one or more tumor types, using the ClinGen/CGC/VICC terminology. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Variant Details

Identifiers

NM_005359.6(SMAD4):c.931C>T (p.Gln311Ter)

Variation ID: 230663 Accession: VCV000230663.7

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 18q21.2 18: 51059892 (GRCh38) [ NCBI UCSC ] 18: 48586262 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	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	May 29, 2016	Jun 9, 2024	Mar 4, 2015
Somatic - Oncogenicity	Aug 11, 2024	Mar 11, 2025	Mar 4, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_005359.6:c.931C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_005350.1:p.Gln311Ter	nonsense
NC_000018.10:g.51059892C>T
NC_000018.9:g.48586262C>T
NG_013013.2:g.96853C>T
LRG_318:g.96853C>T
LRG_318t1:c.931C>T	LRG_318p1:p.Gln311Ter

... more HGVS ... less HGVS

Protein change

Q311*

Other names

Canonical SPDI

NC_000018.10:51059891:C:T

Global minor allele frequency (GMAF) Help The 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA10580984 dbSNP: rs876658694 VarSome

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
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help 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.
SMAD4		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	2620	2664

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 Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Familial thoracic aortic aneurysm and aortic dissection Hereditary cancer-predisposing syndrome	Pathogenic (1)	criteria provided, single submitter	Mar 4, 2015	RCV002310805.9

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.	Expand all rows Collapse all rows Help 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.
Pathogenic (Mar 04, 2015) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Hereditary cancer-predisposing syndrome Familial thoracic aortic aneurysm and aortic dissection Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Ambry Genetics Accession: SCV000274291.7 First in ClinVar: May 29, 2016 Last updated: Jun 09, 2024	Comment: show The p.Q311* pathogenic mutation (also known as c.931C>T) located in coding exon 7 of the SMAD4 gene, results from a C to T substitution at nucleotide position 931. This changes the amino acid from a glutamine to a stop codon within coding exon 7. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

The p.Q311* pathogenic mutation (also known as c.931C>T) located in coding exon 7 of the SMAD4 gene, results from a C to T substitution at nucleotide position 931. This changes the amino acid from a glutamine to a stop codon within coding exon 7. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Conditions - Somatic

Tumor type Help The tumor type for this variant-condition (RCV) record in ClinVar.	Clinical impact (# of submissions) Help The aggregate somatic clinical impact for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate somatic clinical impact is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Oncogenicity Help The aggregate oncogenicity classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to the aggregate oncogenicity classification is shown in parentheses. The corresponding review status for the RCV record is indicated by stars. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the tumor type.	Variation/condition record Help The most recent date that a submitter evaluated this variant for the tumor type.
Neoplasm		Likely oncogenic criteria provided, single submitter	Mar 4, 2025	RCV004668854.2

Submissions - Somatic

Oncogenicity Help The submitted oncogenicity 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)	Tumor type Help The tumor type 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.	Expand all rows Help This column includes more information supporting the somatic clinical impact, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.

Likely oncogenic (Mar 04, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ClinGen/CGC/VICC Guidelines for Oncogenicity, 2022)	Neoplasm	Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital Accession: SCV005093977.2 First In ClinVar: Aug 11, 2024 Last updated: Mar 11, 2025	Publications: PubMed (1) PubMed: 11553622 Observation: 1 Collection method: clinical testing Allele origin: somatic Affected status: yes Observation 1 Collection method: clinical testing Allele origin: somatic Affected status: yes

Comment:

Citations for somatic classification of this variant

Title	Author	Journal	Year	Link
Loss of Smad4 function in pancreatic tumors: C-terminal truncation leads to decreased stability.	Maurice D	The Journal of biological chemistry	2001	PMID: 11553622

Text-mined citations for rs876658694 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated May 17, 2025