ClinVar Miner

Submissions for variant NM_000152.5(GAA):c.953T>C (p.Met318Thr) (rs121907936)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000727662 SCV000854969 uncertain significance not provided 2017-09-27 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000780268 SCV000917391 likely pathogenic Glycogen storage disease, type II 2018-03-09 criteria provided, single submitter clinical testing Variant summary: GAA c.953T>C (p.Met318Thr) results in a non-conservative amino acid change located in the N-terminal of the Glycoside hydrolase family 31 domain (IPR025887) of the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.9e-05 in 263770 control chromosomes (gnomAD and literature). This frequency is not significantly higher than expected for a pathogenic variant in GAA causing Glycogen Storage Disease, Type 2 (Pompe Disease) (4.9e-05 vs 4.20e-03), allowing no conclusion about variant significance. c.953T>C has been reported in the literature individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease), (Zhong_1991, Mori_2017, Loscher_2018). At least one publication reports experimental evidence evaluating an impact on enzyme activity (Zhong_1991). The most pronounced variant effect resulted in <10% of normal activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000004236 SCV000024402 pathogenic Glycogen storage disease type II, infantile 1991-09-01 no assertion criteria provided literature only

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