Submissions for variant NM_000360.4(TH):c.1118C>T (p.Thr373Met)

dbSNP: rs868563700

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001908846	SCV002171342	uncertain significance	Autosomal recessive DOPA responsive dystonia	2022-01-15	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 404 of the TH protein (p.Thr404Met). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with TH-related conditions. 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 TH protein function. 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.
Laboratory Cellgenetics, GMDL Cellgenetics	RCV001908846	SCV003804497	likely pathogenic	Autosomal recessive DOPA responsive dystonia		criteria provided, single submitter	clinical testing	The following ACMG criteria were applied in classifying this variant: PM1, PM2, PP2, PP3, PP4. This variant was detected in compound heterozygous state with c.605G>A (p.Arg202His) variant.
CeGaT Center for Human Genetics Tuebingen	RCV004598159	SCV005092645	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	TH: PM2, PM3, PP3