Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000480433 | SCV000569532 | likely pathogenic | not provided | 2017-07-11 | criteria provided, single submitter | clinical testing | An apparently de novo variant that is likely pathogenic has been identified in the SCN1B gene. The c.108delC variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 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 c.108delC variant causes a frameshift starting with codon Phenylalanine 36, changes this amino acid to a Leucine residue and creates a premature Stop codon at position 111 of the new reading frame, denoted p.Phe36LeufsX111. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. However, frameshift variants have not been reported in the Human Gene Mutation Database in association with SCN1B-related disorders (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Ambry Genetics | RCV001267501 | SCV001445682 | uncertain significance | Inborn genetic diseases | 2019-12-20 | criteria provided, single submitter | clinical testing | The alteration results in a premature stop of translation: The c.108delC (p.F36Lfs*111) alteration, located in coding exon 2 of the SCN1B gene, consists of a deletion of one nucleotide at position 108, causing a translational frameshift with a predicted alternate stop codon after 111 amino acids. Frameshift alterations are typically deleterious in nature (Richards, 2015). The alteration is not observed in population databases: Based on data from the Genome Aggregation Database (gnomAD), the SCN1B c.108delC alteration was not observed, with coverage at this position. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |