ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.457G>A (p.Asp153Asn) (rs72550247)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766769 SCV000223628 uncertain significance not provided 2018-04-19 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN1B gene. The D153N variant was initially published as a pathogenic variant in an individual with atrial fibrillation, and functional studies show that D153N results in lossof function of the protein (Watanabe et al., 2009); however, as seizures were not reported in the affected individual, theassociation of D153N with epilepsy, if any, is unknown. Subsequently, D153N was reported in two individuals who had exome sequencing; the authors classified D153N as a variant of unknown significance (Dorschner et al., 2013). The D153N variant is observed in 7/66,732 (0.01%) alleles from individuals of European background (Lek et al., 2016). The D153N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position in the extracellular domain that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclearwhether this variant is a pathogenic variant or a rare benign variant.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000171064 SCV000540269 uncertain significance not specified 2016-10-20 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 proband with no segregations. In vitro functional study suggests variant results in loss of function; ClinVar: VUS by GeneDx
Ambry Genetics RCV000620098 SCV000737774 uncertain significance Cardiovascular phenotype 2016-11-03 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
OMIM RCV000054538 SCV000083016 pathogenic Atrial fibrillation, familial, 13 2009-06-01 no assertion criteria provided literature only
Forensic Genetics Laboratory,Harris County Institute of Forensic Sciences RCV000234993 SCV000263120 pathogenic Death in early adulthood 2015-03-27 no assertion criteria provided clinical testing NM_001037.4:c.457G>A is pathogenic for Death in early adulthood in combination with NM_198056.2:c.1844G>A

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