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Intellectual disability

Gene: LAMC3

Red List (low evidence)
LAMC3 (laminin subunit gamma 3)
EnsemblGeneIds (GRCh38): ENSG00000050555
EnsemblGeneIds (GRCh37): ENSG00000050555
OMIM: 604349, Gene2Phenotype
LAMC3 is in 6 panels

6 reviews

Arina Puzriakova (Genomics England Curator)

Red List (low evidence)

The rating of this gene has been updated to red and the mode of inheritance updated to BOTH monoallelic and biallelic, autosomal or pseudoautosomal following NHS Genomic Medicine Service approval.
Created: 12 Mar 2026, 1:33 p.m. | Last Modified: 12 Mar 2026, 1:33 p.m.
Panel Version: 9.299
Created: 12 Mar 2026, 1:33 p.m.
Last Modified: 12 Mar 2026, 1:33 p.m.
Panel version: 9.299

Achchuthan Shanmugasundram (Genomics England Curator)

Red List (low evidence)

Comment on list classification: The association of monoallelic variants with intellectual disability is disputed by the expert panel in ClinGen. There is no evidence of ID of moderate severity or worse in patients with biallelic variants. The patients only displayed developmental delay or mild ID. Hence, this gene should be demoted from green rating in the next GMS update.
Created: 22 Oct 2025, 11:52 a.m. | Last Modified: 22 Oct 2025, 11:52 a.m.
Panel Version: 9.146
There are more than 10 unrelated families reported with biallelic variants (either homozygous or compound heterozygous) in LAMC3 and cortical malformations. Although developmental delay or mild intellectual disability (ID) has been reported in several of them, none of them were reported with ID of moderate severity or worse.

PMID:21572413 (2011) - three patients reported of which only one had delayed psychomotor delay.
PMID:26802095 (2016) - borderline - moderate developmental delay reported in several patients from one family.
PMID:29247375 (2018) - global developmental delay and regression reported following seizures in one patient.
PMID:33639934 (2021) - reported foetus with extensive posterior periventricular nodular heterotopia
PMID:34354730 (2021) - no developmental delays reported in the patient.
PMID:38758065 (2024) - four patients reported, of which one patient had mild ID and autism, while another had mild ID.

This gene has also been rated amber with BOTH MOI on 'Intellectual disability syndromic and non-syndromic' panel in PanelApp Australia (https://panelapp-aus.org/panels/250/gene/LAMC3/) Biallelic LAMC3 variants are not yet associated with any relevant phenotypes in ClinGen.

Monoallelic LAMC3 variants are associated with 'complex neurodevelopmental disorder' (MONDO:0100038) with 'Disputed' rating by the Intellectual Disability and Autism expert panel in ClinGen (https://search.clinicalgenome.org/CCID:005265)

This was based on the following evidence:
Although over 25 unique variants have been reported in humans, autism spectrum disorder was the primary ascertainment for the largest number of individuals. Variants have also been reported in probands with intellectual disability and/or developmental delay. However, the variants were primarily identified in individuals with limited phenotype data from large cohort studies, and none had experimental evidence of gene impact (PMIDs: 21572417, 23160955, 27525107, 28191889, 28965761, 30564305, 31398340).
Sources: Literature
Created: 22 Oct 2025, 11:43 a.m. | Last Modified: 22 Oct 2025, 11:43 a.m.
Panel Version: 9.144

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Cortical malformations, occipital, OMIM:614115; occipital pachygyria and polymicrogyria, MONDO:0013583

Publications

Created: 22 Oct 2025, 11:43 a.m.
Last Modified: 22 Oct 2025, 11:43 a.m.
Panel version: 9.145

Eleanor Williams (Genomics England Curator)

Comment on phenotypes: OMIM phenotype accessed on 21st October 2025
Created: 21 Oct 2025, 12:18 p.m. | Last Modified: 21 Oct 2025, 12:18 p.m.
Panel Version: 9.140
Created: 21 Oct 2025, 12:18 p.m.
Last Modified: 21 Oct 2025, 12:18 p.m.
Panel version: 9.140

Caroline Wright (Sanger)

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
OCCIPITAL CORTICAL MALFORMATIONS

Publications

Created: 5 Nov 2017, 2:42 a.m.

Panel version: 0

BRIDGE consortium (NIHRBR-RD)

Green List (high evidence)

This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf;in_gilissen_2014_known . Main mutation mechanism : Loss of function
Created: 27 Jul 2017, 7:11 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; gilissen_2014_known; sfari_20150206; Nijmegen_ID_diagnostic; Nijmegen_ID_candidates; gonzalez_mantilla_2016; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust
Created: 19 Jul 2017, 12:45 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

Created: 2 Aug 2017, 7:56 p.m.

Panel version: 1.354

Lu Raymond (university of cambridge )

Green List (high evidence)

Created: 23 Feb 2016, 10:33 a.m.

Panel version: 0.306

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Red
  • NHS GMS
  • Victorian Clinical Genetics Services
  • Radboud University Medical Center, Nijmegen
Phenotypes
  • Cortical malformations, occipital, OMIM:614115
  • occipital pachygyria and polymicrogyria, MONDO:0013583
OMIM
604349
Clinvar variants
Variants in LAMC3
Penetrance
Complete
Publications
Panels with this gene

History Filter Activity

12 Mar 2026, Gel status: 1

Removed Tag, Removed Tag, Removed Tag

Arina Puzriakova (Genomics England Curator)

Tag Q3_25_MOI was removed from gene: LAMC3. Tag Q3_25_expert_review was removed from gene: LAMC3. Tag Q3_25_demote_red was removed from gene: LAMC3.

12 Mar 2026, Gel status: 1

Added New Source, Added New Source, Set mode of inheritance, Status Update

Arina Puzriakova (Genomics England Curator)

Source NHS GMS was added to LAMC3. Source Expert Review Red was added to LAMC3. Mode of inheritance for gene LAMC3 was changed from BIALLELIC, autosomal or pseudoautosomal to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Rating Changed from Green List (high evidence) to Red List (low evidence)

22 Oct 2025, Gel status: 3

Entity classified by Genomics England curator

Achchuthan Shanmugasundram (Genomics England Curator)

Gene: lamc3 has been classified as Green List (High Evidence).

22 Oct 2025, Gel status: 3

Added Tag, Added Tag, Added Tag

Achchuthan Shanmugasundram (Genomics England Curator)

Tag Q3_25_MOI tag was added to gene: LAMC3. Tag Q3_25_expert_review tag was added to gene: LAMC3. Tag Q3_25_demote_red tag was added to gene: LAMC3.

22 Oct 2025, Gel status: 3

Set publications

Achchuthan Shanmugasundram (Genomics England Curator)

Publications for gene: LAMC3 were set to 21572413; 25529582; 24896178

21 Oct 2025, Gel status: 3

Set publications

Eleanor Williams (Genomics England Curator)

Publications for gene: LAMC3 were set to

21 Oct 2025, Gel status: 3

Set Phenotypes

Eleanor Williams (Genomics England Curator)

Phenotypes for gene: LAMC3 were changed from Cortical malformations, occipital, 614115; OCCIPITAL CORTICAL MALFORMATIONS to Cortical malformations, occipital, OMIM:614115; occipital pachygyria and polymicrogyria, MONDO:0013583

28 Sep 2018, Gel status: 4

Added New Source

Louise Daugherty (Genomics England Curator)

Source Victorian Clinical Genetics Services was added to LAMC3.

12 Mar 2018, Gel status: 3

Panel promoted to version 2.0

Ellen McDonagh (Genomics England Curator)

12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 4

gel status update

GEL ()

The Gel status was updated for this whole panel

13 Nov 2015, Gel status: 1

Set Mode of Inheritance, Added New Source

Ellen McDonagh (Genomics England Curator)

LAMC3 was added to Intellectual disabilitypanel. Source: Expert Review Green Model of inheritance for gene LAMC3 was set to BIALLELIC, autosomal or pseudoautosomal

24 Jun 2015, Gel status: 1

Added New Source

Ellen McDonagh (Genomics England Curator)

LAMC3 was added to Intellectual disabilitypanel. Sources: Radboud University Medical Center, Nijmegen