Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000520201 | SCV000617957 | uncertain significance | not provided | 2023-03-17 | criteria provided, single submitter | clinical testing | The majority of missense variants in this gene are considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This substitution is predicted to be within the extracellular loop between the S5 and S6 transmembrane segments of the third homologous domain; This variant is associated with the following publications: (PMID: 32347949, 18930999) |
Invitae | RCV001088294 | SCV000757709 | likely benign | Early infantile epileptic encephalopathy with suppression bursts | 2023-08-10 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002311841 | SCV000846926 | uncertain significance | Inborn genetic diseases | 2016-06-13 | criteria provided, single submitter | clinical testing | The p.N1391H variant (also known as c.4171A>C), located in coding exon 21 of the SCN1A gene, results from an A to C substitution at nucleotide position 4171. The asparagine at codon 1391 is replaced by histidine, an amino acid with similar properties. A different alteration at the same position, p.N1391S, has been identified in a patient with classic Dravet syndrome (Depienne C et al, J. Med. Genet. 2009 Mar; 46(3):183-91). The p.N1391H variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this variant remains unclear. |
Rady Children's Institute for Genomic Medicine, |
RCV001729621 | SCV001977613 | uncertain significance | SCN1A-related conditions | criteria provided, single submitter | clinical testing | This variant has not been previously reported or functionally characterized in the literature to our knowledge. A different missense change at the same codon (c.4172A>G, p.Asn1391Ser) has been previously reported as a heterozygous change in a patient with Dravet syndrome (PMID: 18930999). It is present in the heterozygous state in the gnomAD population database at a frequency of 0.0004% (1/250566) and thus is presumed to be rare. In silico tools used to predict the effect of this variant on protein function yield discordant results. Based on the available evidence, the c.4171A>C (p.Asn1391His) variant is classified as Variant of Uncertain Significance. |