Submissions for variant NM_001278116.2(L1CAM):c.2302G>A (p.Val768Ile)

gnomAD frequency: 0.00178  dbSNP: rs36021462

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000439917	SCV000110592	uncertain significance	not provided	2014-09-08	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000194324	SCV000247785	likely benign	not specified	2015-11-24	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000194324	SCV000304108	likely benign	not specified		criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000439917	SCV000511247	benign	not provided	2016-09-14	criteria provided, single submitter	clinical testing
Invitae	RCV001083170	SCV000629391	benign	Spastic paraplegia	2024-02-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002313749	SCV000848686	benign	Inborn genetic diseases	2017-01-09	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
GeneDx	RCV000439917	SCV001758011	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30487145, 22222883, 9268105)
Athena Diagnostics Inc	RCV000194324	SCV001879555	benign	not specified	2020-11-19	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000194324	SCV002103477	benign	not specified	2022-02-23	criteria provided, single submitter	clinical testing	Variant summary: L1CAM c.2302G>A (p.Val768Ile) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 204982 control chromosomes, predominantly at a frequency of 0.0063 within the South Asian subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in L1CAM causing L1 Syndrome (0.0021 vs 0.0065), allowing no conclusion about variant significance. Although reported in the literature, to our knowledge, no occurrence/penetrant association of c.2302G>A in individuals affected with L1 Syndrome and no supporting experimental evidence demonstrating its impact on protein function have been reported. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001847649	SCV002105404	likely benign	Hereditary spastic paraplegia	2017-07-18	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000439917	SCV001743567	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000439917	SCV001800356	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000439917	SCV001966258	likely benign	not provided		no assertion criteria provided	clinical testing