ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.448+135del

dbSNP: rs761070541
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521660 SCV000621828 uncertain significance not provided 2017-10-27 criteria provided, single submitter clinical testing The c.583delG variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.583delG variant causes a frameshift starting with codon Glutamic Acid 195, changes this amino acid to an Arginine reside, and creates a premature Stop codon at position 44 of the new reading frame, denotedp.Glu195ArgfsX44. This variant is predicted to cause loss of normal protein function through protein truncation, as the last 74 amino acids are replaced with 43 incorrect amino acids. This variant is not observed in large populationcohorts (Lek et al., 2016). However, other truncating variants downstream of this position have not been reported in the SCN1B gene in association with SCN1B-related disorders (Stenson et al., 2014). Therefore, based on thecurrently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001844186 SCV002104129 uncertain significance not specified 2022-02-21 criteria provided, single submitter clinical testing Variant summary: SCN1B c.583delG (p.Glu195ArgfsX44) results in a premature termination codon, that is not expected to cause nonsense mediated decay (NMD), but is predicted to cause a truncation of the encoded protein, removing amino acids 195 to 268, and replacing it with 43 incorrect amino acids. No truncations downstream of this position have been reported in affected individuals (HGMD). The variant was absent in 236124 control chromosomes (gnomAD). To our knowledge, no occurrence of c.583delG in individuals affected with SCN1B-Related Disorders and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV001853696 SCV002121396 uncertain significance Brugada syndrome 5 2021-06-06 criteria provided, single submitter clinical testing 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 452978). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu195Argfs*44) in the SCN1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 74 amino acid(s) of the SCN1B protein.

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