ClinVar Miner

Submissions for variant NM_000747.3(CHRNB1):c.727C>T (p.Arg243Cys)

dbSNP: rs199875082
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522217 SCV000616677 likely pathogenic not provided 2024-02-07 criteria provided, single submitter clinical testing Reported previously in an abstract using alternate nomenclature (R220C) in an individual with early-onset congenital myasthenia syndrome who also harbored a second variant in the CHRNB1 gene, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Muller JS et al. (2006) Neuromuscular Disorders. 16 (9-10):661 https://www.nmd-journal.com/article/S0960-8966(06)00226-4/fulltext); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 17686188, 34426522, 30290857, Mller2006)
Labcorp Genetics (formerly Invitae), Labcorp RCV000559793 SCV000656607 pathogenic Congenital myasthenic syndrome 2A 2024-01-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 243 of the CHRNB1 protein (p.Arg243Cys). This variant is present in population databases (rs199875082, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive congenital myasthenic syndrome (PMID: 17686188; Invitae). It has also been observed to segregate with disease in related individuals. This variant is also known as R220C. ClinVar contains an entry for this variant (Variation ID: 448999). 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 expected to disrupt CHRNB1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000522217 SCV002545858 likely pathogenic not provided 2022-06-01 criteria provided, single submitter clinical testing CHRNB1: PM3:Strong, PM2

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