Submissions for variant NM_020549.5(CHAT):c.1007T>C (p.Ile336Thr)

dbSNP: rs121912823

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001813998	SCV001755129	likely pathogenic	Abnormality of the musculature	2021-07-10	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000019067	SCV004294368	pathogenic	Familial infantile myasthenia	2023-06-19	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 336 of the CHAT protein (p.Ile336Thr). This variant is present in population databases (rs121912823, gnomAD 0.006%). This missense change has been observed in individuals with congenital myasthenic syndrome (PMID: 12609506). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17515). 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 CHAT protein function. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000019067	SCV005057483	pathogenic	Familial infantile myasthenia	2024-03-28	criteria provided, single submitter	clinical testing
OMIM	RCV000019067	SCV000039354	pathogenic	Familial infantile myasthenia	2003-05-01	no assertion criteria provided	literature only
Neuromuscular Department, Shariati Hospital, Tehran University of Medical Sciences	RCV000019067	SCV001450591	pathogenic	Familial infantile myasthenia	2016-03-03	no assertion criteria provided	clinical testing