VCV000264443.29 - ClinVar

NM_017617.5(NOTCH1):c.6429C>T (p.Asn2143=)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (3); Likely benign (6)

9 out of 12 submissions contributed to this classification

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

No data submitted for oncogenicity

Variant Details

Identifiers

NM_017617.5(NOTCH1):c.6429C>T (p.Asn2143=)

Variation ID: 264443 Accession: VCV000264443.29

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 9q34.3 9: 136497310 (GRCh38) [ NCBI UCSC ] 9: 139391762 (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	Oct 3, 2016	Jul 27, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_017617.5:c.6429C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_060087.3:p.Asn2143=	synonymous
NC_000009.12:g.136497310G>A
NC_000009.11:g.139391762G>A
NG_007458.1:g.53477C>T
LRG_1122:g.53477C>T
LRG_1122t1:c.6429C>T	LRG_1122p1:p.Asn2143=

... more HGVS ... less HGVS

Protein change

Other names

Canonical SPDI

NC_000009.12:136497309:G:A

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.

Exome Aggregation Consortium (ExAC) 0.00012

The Genome Aggregation Database (gnomAD), exomes 0.00019

Trans-Omics for Precision Medicine (TOPMed) 0.00032

The Genome Aggregation Database (gnomAD) 0.00034

The Genome Aggregation Database (gnomAD) 0.00035

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00064

Links

ClinGen: CA5339902 dbSNP: rs369845924 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.
NOTCH1		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	4458	4786

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.
Adams-Oliver syndrome 5	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 4, 2026	RCV000533845.20
Connective tissue disorder	Likely benign (1)	criteria provided, single submitter	Jun 1, 2018	RCV000680583.8
Familial thoracic aortic aneurysm and aortic dissection	Benign/Likely benign (2)	criteria provided, multiple submitters, no conflicts	Feb 27, 2018	RCV001170921.11
not provided	Likely benign (5)	criteria provided, multiple submitters, no conflicts	Dec 1, 2025	RCV001579856.15
Aortic valve disease 1	Benign (1)	criteria provided, single submitter	Mar 15, 2022	RCV002270185.8
NOTCH1-related disorder	Likely benign (1)	no assertion criteria provided	Jun 28, 2021	RCV004542957.2

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.
Likely benign (Jun 01, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Connective tissue disorder	Center for Human Genetics, Inc, Center for Human Genetics, Inc Accession: SCV000808004.1 First in ClinVar: Sep 22, 2018 Last updated: Sep 22, 2018	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Feb 27, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial thoracic aortic aneurysm and aortic dissection	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV001333569.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Sep 08, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000531890.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Mar 15, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Adams-Oliver syndrome 5	Genome-Nilou Lab Accession: SCV002553860.1 First in ClinVar: Jul 30, 2022 Last updated: Jul 30, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Benign (Mar 15, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Aortic valve disease 1	Genome-Nilou Lab Accession: SCV002553861.1 First in ClinVar: Jul 30, 2022 Last updated: Jul 30, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Likely benign (Oct 16, 2015) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Familial thoracic aortic aneurysm and aortic dissection	Ambry Genetics Accession: SCV000320382.7 First in ClinVar: Oct 03, 2016 Last updated: May 01, 2024	Comment: show 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) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely Benign (Feb 19, 2025) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV007331194.1 First in ClinVar: Jan 24, 2026 Last updated: Jan 24, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Adams-Oliver syndrome 5	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000659479.9 First in ClinVar: Dec 26, 2017 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Dec 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV007295182.4 First in ClinVar: Jan 11, 2026 Last updated: Jul 27, 2026	Comment: show NOTCH1: BP4, BP7 (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV001970483.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Jun 28, 2021) N Not contributing to aggregate classification	no assertion criteria provided	NOTCH1-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004780814.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (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

Likely benign (-) N Not contributing to aggregate classification	no assertion criteria provided	not provided	Genome Diagnostics Laboratory, Amsterdam University Medical Center Study: VKGL Data-share Consensus Accession: SCV001808761.1 First in ClinVar: Aug 26, 2021 Last updated: Aug 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

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 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.

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.

Text-mined citations for rs369845924 ...

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 Jul 27, 2026