Submissions for variant NM_001278116.2(L1CAM):c.2537G>T (p.Arg846Leu)

gnomAD frequency: 0.00009  dbSNP: rs149737236

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000431818	SCV000527090	likely benign	not specified	2016-05-02	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847778	SCV002105407	uncertain significance	Hereditary spastic paraplegia	2016-12-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453468	SCV002740060	likely benign	Inborn genetic diseases	2018-09-22	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: 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.
Invitae	RCV002515965	SCV002996686	benign	Spastic paraplegia	2024-01-11	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000146245	SCV000595475	uncertain significance	Hydrocephalus due to aqueductal stenosis	2016-01-05	no assertion criteria provided	clinical testing	DNA sequence analysis of the L1CAM gene demonstrated a sequence change, c.2537G>T, in exon 19 that results in an amino acid change, p.Arg846Leu. This sequence change does not appear to have been previously described in patients with L1CAM-related disorders and has been described in the EXAC database with a low population frequency of 0.009% (dbSNP rs149737236). The p.Arg846Leu change affects a highly conserved amino acid residue located in a domain of the L1CAM protein that is known to be functional. The p.Arg846Leu substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Arg846Leu change remains unknown at this time.