ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.38T>C (p.Leu13Pro) (rs786205834)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766768 SCV000223614 uncertain significance not provided 2017-07-10 criteria provided, single submitter clinical testing The L13P 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 1,100 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 L13P 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 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. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Genetic Services Laboratory, University of Chicago RCV000192329 SCV000248799 uncertain significance not specified 2015-04-16 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000192329 SCV000615051 uncertain significance not specified 2017-07-20 criteria provided, single submitter clinical testing
Invitae RCV000687916 SCV000815509 uncertain significance Brugada syndrome 5 2018-05-12 criteria provided, single submitter clinical testing This sequence change replaces leucine with proline at codon 13 of the SCN1B protein (p.Leu13Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with SCN1B-related disease. ClinVar contains an entry for this variant (Variation ID: 190870). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV000720439 SCV000851316 uncertain significance Seizures 2017-08-31 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence,In silico models in agreement (benign)
Fulgent Genetics,Fulgent Genetics RCV000765437 SCV000896726 uncertain significance Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Epileptic encephalopathy, early infantile, 52 2018-10-31 criteria provided, single submitter clinical testing

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