Submissions for variant NM_006996.3(SLC19A2):c.1214C>G (p.Thr405Arg)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003709861	SCV004475546	likely pathogenic	not provided	2023-09-05	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 SLC19A2 protein function. This missense change has been observed in individual(s) with thiamine-responsive megaloblastic anemia (PMID: 35990029). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs554433074, gnomAD 0.007%). This sequence change replaces threonine, which is neutral and polar, with arginine, which is basic and polar, at codon 405 of the SLC19A2 protein (p.Thr405Arg).