ClinVar Miner

Submissions for variant NM_002977.3(SCN9A):c.2987G>A (p.Arg996His) (rs188145203)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000478443 SCV000855945 likely benign not specified 2017-08-08 criteria provided, single submitter clinical testing
GeneDx RCV000478443 SCV000565541 uncertain significance not specified 2016-06-20 criteria provided, single submitter clinical testing The R996H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. However, a different amino acid substitution at the same position (R966C) has been previously reported in two families with mild paroxysmal extreme pain disorder (PEPD) (Fertleman et al., 2006). However, the 1000 Genomes Project reports R996H was observed in 6/226 (2.7%) alleles from individuals of Gambian background, including one homozygous individual; it was not observed with any significant frequency in approximately 5,800 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The R996H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved, and Histidine is observed at this position in other species. In silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000308517 SCV000418501 likely benign Inherited Erythromelalgia 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000365438 SCV000418502 likely benign Familial Febrile Seizures 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000273253 SCV000418503 likely benign Generalized epilepsy with febrile seizures plus 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000330258 SCV000418504 likely benign Small fiber neuropathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000368610 SCV000418505 likely benign Paroxysmal extreme pain disorder 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000276406 SCV000418506 likely benign Severe myoclonic epilepsy in infancy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000333798 SCV000418507 likely benign Congenital Indifference to Pain 2016-06-14 criteria provided, single submitter clinical testing

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