VCV000226120.3 - ClinVar

NM_001278116.2(L1CAM):c.2380C>T (p.Gln794Ter)

Germline

Classification

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

Pathogenic/Likely pathogenic

2 out of 2 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_001278116.2(L1CAM):c.2380C>T (p.Gln794Ter)

Variation ID: 226120 Accession: VCV000226120.3

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq28 X: 153866700 (GRCh38) [ NCBI UCSC ] X: 153132155 (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 21, 2016	Apr 13, 2025	Apr 7, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_001278116.2:c.2380C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001265045.1:p.Gln794Ter	nonsense
NM_000425.5:c.2380C>T	NP_000416.1:p.Gln794Ter	nonsense
NM_001143963.2:c.2365C>T	NP_001137435.1:p.Gln789Ter	nonsense
NM_024003.3:c.2380C>T	NP_076493.1:p.Gln794Ter	nonsense
NC_000023.11:g.153866700G>A
NC_000023.10:g.153132155G>A
NG_009645.3:g.47524C>T
LRG_14t1:c.2380C>T	LRG_14p1:p.Gln794Ter
LRG_14t2:c.2380C>T	LRG_14p2:p.Gln794Ter

... more HGVS ... less HGVS

Protein change

Q794*, Q789*

Other names

Canonical SPDI

NC_000023.11:153866699: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.

Links

ClinGen: CA10576254 dbSNP: rs875989884 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.
L1CAM		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1531	1809

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.
X-linked hydrocephalus syndrome	Pathogenic (1)	criteria provided, single submitter	Apr 5, 2016	RCV000211546.2
L1 syndrome	Likely pathogenic (1)	criteria provided, single submitter	Apr 7, 2022	RCV002229193.1

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.	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 pathogenic (Apr 07, 2022) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	L1 syndrome	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV002511499.1 First in ClinVar: May 16, 2022 Last updated: May 16, 2022	Comment: show Variant summary: L1CAM c.2380C>T (p.Gln794X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 183249 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2380C>T in individuals affected with L1 Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. (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

Pathogenic (Apr 05, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	X-linked hydrocephalus syndrome	Center of Genomic medicine, Geneva, University Hospital of Geneva Accession: SCV000268523.2 First in ClinVar: May 21, 2016 Last updated: Apr 13, 2025	Comment: show The L1CAM pathogenic mutation was observed in a patient with hydrocephalus due to aqueductal stenosis. (less) Observation: 1 Collection method: clinical testing Allele origin: maternal Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: maternal Affected status: yes Age: 0-1 years Sex: male

Comment:

Variant summary: L1CAM c.2380C>T (p.Gln794X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 183249 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2380C>T in individuals affected with L1 Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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 rs875989884 ...

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 Dec 20, 2025