ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5951C>A (p.Pro1984His) (rs146733308)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000723619 SCV000111475 uncertain significance not provided 2013-04-19 criteria provided, single submitter clinical testing
GeneDx RCV000189028 SCV000242659 uncertain significance not specified 2017-07-21 criteria provided, single submitter clinical testing p.Pro1984His (CCT>CAT): c.5951 C>A in exon 26 of the SCN1A gene (NM_001165963.1) The Pro1984His missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It has been identified on 12/4406 alleles in individuals of African American ancestry in the NHLBI Exome Sequencing Project and 1/110 alleles in individuals of Puerto Rican ancestry in the 1000 Genomes Project. Additionally, it was previously identified at GeneDx in unreleated individuals who had a disease-causing mutations in different genes on the Epilepsy Panel. The Pro1984His amino acid substitution is non-conservative, as an uncharged, non-polar Proline residue is replaced by a positively charged Histidine residue, and the loss of a bulky Proline residue may alter the secondary structure of the protein. It alters a highly conserved position in the C-terminal region of the protein, and multiple in silico algorithms predict it may be damaging to protein structure/function. Therefore, based on the currently available information, it is unclear whether Pro1984His is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY,INFANT-EPI panel(s).
Ambry Genetics RCV000716817 SCV000847661 benign History of neurodevelopmental disorder 2019-03-07 criteria provided, single submitter clinical testing General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Fulgent Genetics,Fulgent Genetics RCV000764282 SCV000895301 uncertain significance Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV001080157 SCV001008820 likely benign Early infantile epileptic encephalopathy 2019-12-31 criteria provided, single submitter clinical testing

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