ClinVar Miner

Submissions for variant NM_001278116.2(L1CAM):c.1108G>A (p.Gly370Arg) (rs137852524)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255983 SCV000321853 pathogenic not provided 2016-07-26 criteria provided, single submitter clinical testing The G370R pathogenic variant in the L1CAM gene has been reported previously in a family with multiple affected males with clinical features ranging from hydrocephalus to MASA syndrome (Ruiz et al., 1995). Additionally, this variant has been shown to reduce ligand binding in the functional Ig4 domain of the protein (De Angelis et al., 2002). The G370R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G370R variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret G370R as a pathogenic variant.
Invitae RCV000815545 SCV000956005 pathogenic Spastic paraplegia 2019-06-21 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 370 of the L1CAM protein (p.Gly370Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with L1 syndrome in a family (PMID: 7562969,8062435). ClinVar contains an entry for this variant (Variation ID: 9995). This variant has been reported to affect L1CAM protein function (PMID: 11772994). For these reasons, this variant has been classified as Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001198070 SCV001368855 pathogenic Dandy-Walker syndrome; Cerebral atrophy; Partial agenesis of the corpus callosum; Macrocephalus; Absent septum pellucidum; Severe hydrocephalus; Aplasia/Hypoplasia of the cerebellum; Enlarged fetal cisterna magna 2016-01-01 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP3. This variant was detected in heterozygous state.
OMIM RCV000010677 SCV000030903 pathogenic MASA syndrome 1995-07-01 no assertion criteria provided literature only

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