Submissions for variant NM_000079.4(CHRNA1):c.410C>T (p.Thr137Met)

gnomAD frequency: 0.00003  dbSNP: rs780391418

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000488357	SCV000575262	uncertain significance	not provided	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV003517202	SCV004299200	uncertain significance	Lethal multiple pterygium syndrome	2023-10-24	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 137 of the CHRNA1 protein (p.Thr137Met). This variant is present in population databases (rs780391418, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with CHRNA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 425235). 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 CHRNA1 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.
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000781968	SCV000920423	uncertain significance	Epilepsy	2016-09-06	no assertion criteria provided	clinical testing
Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital	RCV000781969	SCV000920424	uncertain significance	Seizure	2016-09-06	no assertion criteria provided	clinical testing