Submissions for variant NM_000152.5(GAA):c.704C>T (p.Thr235Met)

gnomAD frequency: 0.00001  dbSNP: rs752950890

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000813790	SCV000954163	uncertain significance	Glycogen storage disease, type II	2022-04-21	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 235 of the GAA protein (p.Thr235Met). This variant is present in population databases (rs752950890, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with GAA-related conditions. ClinVar contains an entry for this variant (Variation ID: 657223). 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 GAA 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.
CeGaT Center for Human Genetics Tuebingen	RCV001090257	SCV001245685	uncertain significance	not provided	2020-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000813790	SCV002027233	uncertain significance	Glycogen storage disease, type II	2021-09-05	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000813790	SCV002091954	uncertain significance	Glycogen storage disease, type II	2021-03-11	no assertion criteria provided	clinical testing