ClinVar Miner

Submissions for variant NM_000744.7(CHRNA4):c.919G>A (p.Gly307Ser)

dbSNP: rs764586079
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000186932 SCV000240503 uncertain significance not provided 2013-05-17 criteria provided, single submitter clinical testing p.Gly307Ser (GGC>AGC): c.919 G>A in exon 5 of the CHRNA4 gene (NM_000744.5)The Gly307Ser missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 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 amino acid substitution is non-conservative as a non-polar Glycine residue is replaced by a polar Serine residue. Gly307Ser alters a highly conserved position in the CHRNA4 protein and multiple in-silico algorithms predict it may be damaging to protein structure/function. However, this amino acid substitution does not occur within the transmembrane region of the protein, where most pathogenic missense mutations have been identified in association with epilepsy (Steinlein et al., 2010). Therefore, based on the currently available information, it is unclear whether Gly307Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).
Centogene AG - the Rare Disease Company RCV001808464 SCV002059241 uncertain significance Autosomal dominant nocturnal frontal lobe epilepsy 1 2018-01-03 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002517845 SCV003511627 likely benign Autosomal dominant nocturnal frontal lobe epilepsy 2024-01-18 criteria provided, single submitter clinical testing
Ambry Genetics RCV003278686 SCV003984704 uncertain significance Inborn genetic diseases 2023-05-28 criteria provided, single submitter clinical testing The c.919G>A (p.G307S) alteration is located in exon 5 (coding exon 5) of the CHRNA4 gene. This alteration results from a G to A substitution at nucleotide position 919, causing the glycine (G) at amino acid position 307 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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