Submissions for variant NM_005562.3(LAMC2):c.3385C>T (p.Arg1129Ter)

dbSNP: rs201307156

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000411632	SCV000486392	likely pathogenic	Junctional epidermolysis bullosa gravis of Herlitz	2016-05-24	criteria provided, single submitter	clinical testing
Invitae	RCV001386477	SCV001586711	pathogenic	not provided	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1129*) in the LAMC2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 65 amino acid(s) of the LAMC2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with LAMC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 370953). This variant disrupts a region of the LAMC2 protein in which other variant(s) (p.Thr1132Asnfs*38) have been determined to be pathogenic (PMID: 11564184). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Department of Pediatrics, Division of Medical Genetics, Faculty of Medicine Ramathibodi Hospital, Mahidol University	RCV001731663	SCV001983770	pathogenic	Junctional epidermolysis bullosa, non-Herlitz type	2020-12-08	no assertion criteria provided	research