Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000497542 | SCV000589692 | uncertain significance | not provided | 2017-06-15 | criteria provided, single submitter | clinical testing | The M235T variant in the L1CAM gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M235T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M235T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret M235T as a variant of uncertain significance. |
| Geisinger Autism and Developmental Medicine Institute, |
RCV000678319 | SCV000804378 | uncertain significance | X-linked hydrocephalus syndrome | 2018-03-06 | criteria provided, single submitter | provider interpretation | This variant was identified in a 12 year old male with mild intellectual disability, motor speech disorder, adaptive deficits, dyspraxia, hypotonia, ADHD, bifid uvula, mild dolichocephaly, large ears, mild pectus excavatum, hypoplastic nipples, and slightly tapered fingers. This variant is absent from the gnomAD database. Computational prediction models are inconsistent. This variant has not been reported previously in the literature, to our knowledge. This variant was also present in the proband's healthy, adult brother, making it unlikely to be an explanation for the proband's history. Additionally, whole exome sequencing also identified two additional variants of uncertain significance. |