NM_000642.3(AGL):c.3635T>C (p.Met1212Thr) AND Glycogen storage disease type III

Clinical significance:Uncertain significance (Last evaluated: Apr 10, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000642.3(AGL):c.3635T>C (p.Met1212Thr)]

NM_000642.3(AGL):c.3635T>C (p.Met1212Thr)

AGL:amylo-alpha-1, 6-glucosidase, 4-alpha-glucanotransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000642.3(AGL):c.3635T>C (p.Met1212Thr)
  • NC_000001.11:g.99902729T>C
  • NG_012865.1:g.57646T>C
  • NM_000028.2:c.3635T>C
  • NM_000642.3:c.3635T>CMANE SELECT
  • NM_000643.2:c.3635T>C
  • NM_000644.2:c.3635T>C
  • NM_000646.2:c.3587T>C
  • NP_000019.2:p.Met1212Thr
  • NP_000633.2:p.Met1212Thr
  • NP_000634.2:p.Met1212Thr
  • NP_000635.2:p.Met1212Thr
  • NP_000637.2:p.Met1196Thr
  • NC_000001.10:g.100368285T>C
  • NM_000642.2:c.3635T>C
Protein change:
dbSNP: rs779439947
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000028.2:c.3635T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000642.3:c.3635T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000643.2:c.3635T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000644.2:c.3635T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_000646.2:c.3587T>C - missense variant - [Sequence Ontology: SO:0001583]


Glycogen storage disease type III (GSD3)
Glycogen storage disease type 3; Forbes disease; Cori disease; See all synonyms [MedGen]
MONDO: MONDO:0009291; MedGen: C0017922; Orphanet: 366; OMIM: 232400

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000626732Invitaecriteria provided, single submitter
Uncertain significance
(Apr 10, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

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



Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Invitae, SCV000626732.1

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


This sequence change replaces methionine with threonine at codon 1212 of the AGL protein (p.Met1212Thr). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is present in population databases (rs779439947, ExAC 0.009%) but has not been reported in the literature in individuals with a AGL-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Nov 27, 2021

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