Malformations of cortical development

Gene: LAMC3

Green List (high evidence)

Comment on list classification: The 'Disputed' rating on ClinGen is only relevant for monoallelic MOI. As there is sufficient evidence available for the association of biallelic variants with the phenotype, this gene should remain green with biallelic MOI on this panel.

Created: 23 Oct 2025, 11:52 a.m. | Last Modified: 23 Oct 2025, 11:53 a.m.

Panel Version: 7.12

There are seven unrelated families reported with biallelic variants (either homozygous or compound heterozygous) in LAMC3 and cortical malformations.

Biallelic LAMC3 variants are associated with relevant phenotypes in OMIM (MIM #614115, record accessed on 21 October 2025) and Gene2Phenotype (with 'definitive' rating on the DD panel). 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).

Created: 21 Oct 2025, 12:05 p.m. | Last Modified: 23 Oct 2025, 11:50 a.m.

Panel Version: 7.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

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

Publications

• 21572413
• 26802095
• 29247375
• 33639934
• 34354730

Comment when marking as ready: Recognised on G2P. Expert review green. Offered on UKGTN

Created: 19 Dec 2016, 10:40 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Occipital cortical malformations

Variants in this GENE are reported as part of current diagnostic practice