ClinVar Miner

Submissions for variant NM_001037.5(SCN1B):c.448+193G>A (rs66876876)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 13
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000171026 SCV000050835 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
GeneDx RCV000212986 SCV000223590 likely benign not specified 2018-01-26 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000171026 SCV000291890 benign not provided 2019-02-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000212986 SCV000342754 likely benign not specified 2016-06-17 criteria provided, single submitter clinical testing
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000171026 SCV000511289 likely benign not provided 2016-12-05 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000212986 SCV000540265 benign not specified 2016-03-28 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: ExAC: 1.4% (5/344) Finnish chromosomes
Phosphorus, Inc. RCV000578074 SCV000679977 uncertain significance Atrial fibrillation, familial, 13 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000226296 SCV000679978 uncertain significance Brugada syndrome 5 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578041 SCV000679979 uncertain significance Epileptic encephalopathy, early infantile, 52 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578118 SCV000679980 uncertain significance Generalized epilepsy with febrile seizures plus, type 1 2017-08-01 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000171026 SCV000892240 likely benign not provided 2018-09-30 criteria provided, single submitter clinical testing
Stanford Center for Inherited Cardiovascular Disease, Stanford University RCV000212986 SCV000280461 uncertain significance not specified 2014-12-04 no assertion criteria provided clinical testing Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Arg214Gln (c.641 G>A) in the SCN1B gene: The missense p.Arg214Gln variant has been previously reported in six unrelated individuals with BrS, all of whom are of European descent. Hu et al. reported it in two unrelated individuals of European descent with BrS and one child who died from SIDS (Hu et al, 2012) from a cohort of 476 (frequency 0.63%) patients with Brugada syndrome or SIDS. This variant was not seen in 476 ethnically matched controls with BrS, although Hu et al., (2012) did report that this variant had previously been seen in 4 of 807 (frequency 0.49%) ethnically matched controls in a separate dataset. Additionally, it was noted that each of these individuals also had one common polymorphism in the SCN1B gene (L210P, S248R and R250T). This variant was thought to interfere with sodium current density (Hu et al., 2012). This variant has also been reported in one Danish patient from a cohort of 42 (frequency 2.38%) Danish individuals with BrS (Holst et al., 2012). This affected individual did not have any other family members with BrS and segregation data was not available. The variant was absent in 216 ethnically similar controls in this study. This p.Arg214Gln variant has also been seen in a single patient from a cohort of 129 (frequency 0.77%) American and Italian patients with BrS (Crotti et al., 2012). It was seen in one individual in a cohort of 145 (frequency 0.69%) Italian patients with BrS (Ricci et al., 2014). Finally, this variant was seen in a single individual with BrS from a cohort of 22 (frequency 4.54%) Danish individuals with BrS (Oleson et al., 2012). It was not seen in 216 ethnically matched controls. p.Arg214Gln has also been seen in individuals with epilepsy and AF. It was reported in one patient with epilepsy out of a cohort of 360 (frequency 0.27%) American individuals with epilepsy (Patino et al., 2011). It was also seen in two individuals with AF in Denmark. This variant was not seen in 216 ethnically similar controls in this study (Oleson et al., 2012). The p.Arg214Gln variant results in a semi-conservative amino acid change from a positively charged Arginine to a polar Glutamine. The UCSC Genome Browser indicates that the Arginine amino acid is highly conserved from humans to primates. It is not conserved in all vertebrates. Glutamine is in fact the default amino acid in mice, rat & elephant. Additionally, the amino acids surrounding this Arginine are highly conserved through primates but not through all vertebrates. In silico analysis with Polyphen-2, SIFT and Mutation Taster are all consistent and predict this variant to be benign. In total, this variant has been seen in 27 out of ~5,200 controls (1,700 from published literature described above and 3,500 from NHLBI). The NHLBI Exome Sequencing Project dataset currently includes variant calls on 2,237 Caucasian and 1,241 African American individuals for this variant (as of 10/23/14). This variant was seen in a total of 21 European American individuals and 2 African American individuals (overall frequency 0.66%, Caucasian frequency almost 1%). There is no variation at this codon listed in 1000 genomes (as of 10/23/14). Variation at this codon is seen in the ExAC Browser dataset, which currently includes variant calls on 26,976 individuals of multiple ethnic backgrounds. It is particularly frequent among Caucasians. This variant was seen in a total of 87 individuals of Finnish(6), European(76), Latino(2), African(1) and South Asian(2) descent (frequency 0.33%) (as of 10/23/14).
GenomeConnect, ClinGen RCV000171026 SCV000606919 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.