Submissions for variant NM_000152.5(GAA):c.1343G>C (p.Ser448Thr)

gnomAD frequency: 0.00057  dbSNP: rs145712232

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000359113	SCV000335652	likely benign	not specified	2015-10-07	criteria provided, single submitter	clinical testing
Invitae	RCV000531819	SCV000626508	benign	Glycogen storage disease, type II	2024-01-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000359113	SCV000714405	likely benign	not specified	2017-10-16	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego	RCV000852732	SCV000995447	benign	Primary dilated cardiomyopathy	2018-01-05	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000359113	SCV001426835	benign	not specified	2020-07-30	criteria provided, single submitter	clinical testing	Variant summary: GAA c.1343G>C (p.Ser448Thr) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0011 in 250344 control chromosomes, predominantly at a frequency of 0.008 within the South Asian subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 2 fold of the estimated maximal expected allele frequency for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) phenotype (0.0042), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. To our knowledge, no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000531819	SCV004564191	benign	Glycogen storage disease, type II	2023-11-29	criteria provided, single submitter	clinical testing