Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001174962 | SCV001338444 | pathogenic | Glycogen storage disease, type II | 2020-04-30 | criteria provided, single submitter | clinical testing | Variant summary: GAA c.1634C>T (p.Pro545Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 250468 control chromosomes. c.1634C>T has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease, Vorgerd_1998, Flanagan_2009, vanCapelle_2016). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity (Flanagan_2009). 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 pathogenic. |
Revvity Omics, |
RCV001785449 | SCV002021171 | pathogenic | not provided | 2021-10-12 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001174962 | SCV002213638 | pathogenic | Glycogen storage disease, type II | 2023-07-25 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 4032). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects GAA function (PMID: 7881422). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. This missense change has been observed in individuals with glycogen storage disease type II (PMID: 7881422, 14695532, 25526786). This variant is present in population databases (rs121907942, gnomAD 0.01%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 545 of the GAA protein (p.Pro545Leu). |
Baylor Genetics | RCV001174962 | SCV004197837 | pathogenic | Glycogen storage disease, type II | 2023-05-04 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000004247 | SCV000024413 | pathogenic | Glycogen storage disease II, adult form | 1994-12-01 | no assertion criteria provided | literature only | |
Natera, |
RCV001174962 | SCV002092051 | pathogenic | Glycogen storage disease, type II | 2020-12-15 | no assertion criteria provided | clinical testing |