Submissions for variant NM_001037.5(SCN1B):c.448+4_448+12del

dbSNP: rs1322172446

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598805	SCV000710737	uncertain significance	not provided	2023-01-09	criteria provided, single submitter	clinical testing	Intronic +5 splice site variant in a gene for which loss-of-function is a known mechanism of disease, and both splice predictors and evolutionary conservation support a deleterious effect, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002331027	SCV002636974	uncertain significance	Cardiovascular phenotype	2019-06-28	criteria provided, single submitter	clinical testing	The c.448+4_448+12delAGTCGGGTG intronic variant, located in intron 3 of the SCN1B gene, results from a deletion of 9 nucleotides within intron 3 of the SCN1B gene. These nucleotide positions are not well conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to weaken the efficiency of the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003767421	SCV004663038	uncertain significance	Brugada syndrome 5	2023-10-10	criteria provided, single submitter	clinical testing	This variant, c.452_460del, results in the deletion of 3 amino acid(s) of the SCN1B protein (p.Glu151_Gly153del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 504415). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.