Submissions for variant NM_001032283.3(TMPO):c.565+1374A>C

dbSNP: rs760685984

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000549718	SCV000646404	uncertain significance	Loeys-Dietz syndrome 2	2017-06-21	criteria provided, single submitter	clinical testing	In summary, this variant has uncertain impact on TMPO function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The proline amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with a TMPO-related disease. This variant is present in population databases (rs760685984, ExAC 0.009%). This sequence change replaces threonine with proline at codon 319 of the TMPO protein (p.Thr319Pro). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and proline.