NM_000152.5(GAA):c.1115A>T (p.His372Leu) AND Glycogen storage disease, type II

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Oct 18, 2019)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000411518.2

Allele description [Variation Report for NM_000152.5(GAA):c.1115A>T (p.His372Leu)]

NM_000152.5(GAA):c.1115A>T (p.His372Leu)

Gene:
GAA:alpha glucosidase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q25.3
Genomic location:
Preferred name:
NM_000152.5(GAA):c.1115A>T (p.His372Leu)
HGVS:
  • NC_000017.11:g.80108528A>T
  • NG_009822.1:g.11973A>T
  • NM_000152.5:c.1115A>TMANE SELECT
  • NM_001079803.3:c.1115A>T
  • NM_001079804.3:c.1115A>T
  • NP_000143.2:p.His372Leu
  • NP_001073271.1:p.His372Leu
  • NP_001073272.1:p.His372Leu
  • LRG_673t1:c.1115A>T
  • LRG_673:g.11973A>T
  • NC_000017.10:g.78082327A>T
  • NM_000152.3:c.1115A>T
  • NM_000152.4:c.1115A>T
Protein change:
H372L
Links:
dbSNP: rs1057516520
NCBI 1000 Genomes Browser:
rs1057516520
Molecular consequence:
  • NM_000152.5:c.1115A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079803.3:c.1115A>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001079804.3:c.1115A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Glycogen storage disease, type II (GSD2)
Synonyms:
ACID ALPHA-GLUCOSIDASE DEFICIENCY; GLYCOGENOSIS, GENERALIZED, CARDIAC FORM; GSD II; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009290; MedGen: C0017921; Orphanet: 365; OMIM: 232300

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000485819Counsylcriteria provided, single submitter
Likely pathogenic
(Feb 18, 2016)
unknownclinical testing

PubMed (3)
[See all records that cite these PMIDs]

mdi-5618_320494_Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015).pdf,

Citation Link,

SCV001362545Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Oct 18, 2019)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Effect of enzyme therapy in juvenile patients with Pompe disease: a three-year open-label study.

van Capelle CI, van der Beek NA, Hagemans ML, Arts WF, Hop WC, Lee P, Jaeken J, Frohn-Mulder IM, Merkus PJ, Corzo D, Puga AC, Reuser AJ, van der Ploeg AT.

Neuromuscul Disord. 2010 Dec;20(12):775-82. doi: 10.1016/j.nmd.2010.07.277.

PubMed [citation]
PMID:
20817528

Clinical and Molecular Characterization of Infantile-Onset Pompe Disease in Mainland Chinese Patients: Identification of Two Common Mutations.

Chen X, Liu T, Huang M, Wu J, Zhu J, Guo Y, Xu X, Li F, Wang J, Fu L.

Genet Test Mol Biomarkers. 2017 Jun;21(6):391-396. doi: 10.1089/gtmb.2016.0424. Epub 2017 Apr 10.

PubMed [citation]
PMID:
28394184
See all PubMed Citations (7)

Details of each submission

From Counsyl, SCV000485819.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362545.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: GAA c.1115A>T (p.His372Leu) results in a non-conservative amino acid change located in the Glycoside hydrolase family 31 domain (IPR000322) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248930 control chromosomes (gnomAD). c.1115A>T has been reported in the literature in individuals affected with Glycogen Storage Disease, Type 2 (Pompe Disease) (VandenHout__2004, Joshi_2008, vanGelder_2014, Chen_2017, Lin_2017, Lee_2019). These data indicate that the variant is likely to be associated with disease. Two publications report this variant has an impact on protein function and results in <10% of normal GAA activity (VandenHout__2004, Lin_2017). One ClinVar submitter (evaluation after 2014) cites the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 14, 2021

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