Submissions for variant NM_000748.3(CHRNB2):c.329A>C (p.Lys110Thr)

gnomAD frequency: 0.00002  dbSNP: rs199885651

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000186986	SCV000240559	uncertain significance	not provided	2020-11-03	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000416529	SCV000494437	uncertain significance	Seizure; Deeply set eye; Microcephaly	2016-02-23	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001213692	SCV001385338	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy	2024-05-28	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with threonine, which is neutral and polar, at codon 110 of the CHRNB2 protein (p.Lys110Thr). This variant is present in population databases (rs199885651, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with CHRNB2-related conditions. ClinVar contains an entry for this variant (Variation ID: 205066). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHRNB2 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Institute of Human Genetics, University of Leipzig Medical Center	RCV001262983	SCV001441049	uncertain significance	Autosomal dominant nocturnal frontal lobe epilepsy 3	2019-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002513986	SCV003603893	likely benign	Inborn genetic diseases	2021-12-20	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000186986	SCV004124858	uncertain significance	not provided	2023-03-01	criteria provided, single submitter	clinical testing	CHRNB2: PP2