Submissions for variant NM_000744.7(CHRNA4):c.1175C>T (p.Pro392Leu)

dbSNP: rs2123471262

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Neuberg Centre For Genomic Medicine, NCGM	RCV001823437	SCV002072873	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 1		criteria provided, single submitter	clinical testing	The missense variant p.P392L in CHRNA4 (NM_000744.7) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.P392L variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. There is a moderate physicochemical difference between proline and leucine. In silico tools predict the variant to be tolearted and the residue is conserved across species. For these reasons, this variant has been classified as Uncertain Significance
Neuberg Centre For Genomic Medicine, NCGM	RCV002510596	SCV002820291	uncertain significance	Developmental and epileptic encephalopathy 94		criteria provided, single submitter	clinical testing	The missense variant p.V230I in CHD2 (NM_001271.4) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. It has been submitted to ClinVar as Uncertain significance. The missense variant c.688G>A (p.V230I) in CHD2 (NM_001271.4) is observed in 3/34404 (0.0087%) alleles from individuals of Latino background in the gnomAD dataset (Exome Aggregation Consortium et al., 2016), but was not seen in the homozygous state. For these reasons, this variant has been classified as Uncertain Significance