NM_000036.2(AMPD1):c.567G>T (p.Gln189His) AND Muscle AMP deaminase deficiency

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(2);Uncertain significance(1) (Last evaluated: Mar 24, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000763230.5

Allele description [Variation Report for NM_000036.2(AMPD1):c.567G>T (p.Gln189His)]

NM_000036.2(AMPD1):c.567G>T (p.Gln189His)

Gene:
AMPD1:adenosine monophosphate deaminase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p13.2
Genomic location:
Preferred name:
NM_000036.2(AMPD1):c.567G>T (p.Gln189His)
HGVS:
  • NC_000001.11:g.114684278C>A
  • NG_008012.1:g.16278G>T
  • NM_000036.2:c.567G>T
  • NM_001172626.1:c.555G>T
  • NP_000027.2:p.Gln189His
  • NP_001166097.1:p.Gln185His
  • NC_000001.10:g.115226899C>A
Protein change:
Q185H
Links:
dbSNP: rs139582106
NCBI 1000 Genomes Browser:
rs139582106
Molecular consequence:
  • NM_000036.2:c.567G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001172626.1:c.555G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Muscle AMP deaminase deficiency (MMDD)
Synonyms:
Myoadenylate deaminase deficiency, myopathy due to; Adenosine monophosphate deaminase 1 deficiency; AMP deaminase 1 deficiency; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0014220; MedGen: C3714933; Orphanet: 45; OMIM: 615511

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000893863Fulgent Genetics,Fulgent Geneticscriteria provided, single submitter
Likely pathogenic
(Oct 31, 2018)
unknownclinical testing

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

SCV000932594Invitaecriteria provided, single submitter
Uncertain significance
(Apr 16, 2019)
germlineclinical testing

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

SCV001366486Centre for Mendelian Genomics,University Medical Centre Ljubljanacriteria provided, single submitter
Likely pathogenic
(Mar 24, 2020)
unknownclinical 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
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Rare variants in known and novel candidate genes predisposing to statin-associated myopathy.

Neřoldová M, Stránecký V, Hodaňová K, Hartmannová H, Piherová L, Přistoupilová A, Mrázová L, Vrablík M, Adámková V, Hubáček JA, Jirsa M, Kmoch S.

Pharmacogenomics. 2016 Aug;17(13):1405-14. doi: 10.2217/pgs-2016-0071. Epub 2016 Jun 14.

PubMed [citation]
PMID:
27296017

A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.

Gross M, Rötzer E, Kölle P, Mortier W, Reichmann H, Goebel HH, Lochmüller H, Pongratz D, Mahnke-Zizelman DK, Sabina RL.

Neuromuscul Disord. 2002 Aug;12(6):558-65.

PubMed [citation]
PMID:
12117480
See all PubMed Citations (4)

Details of each submission

From Fulgent Genetics,Fulgent Genetics, SCV000893863.1

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

From Invitae, SCV000932594.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glutamine with histidine at codon 189 of the AMPD1 protein (p.Gln189His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine. This variant is present in population databases (rs139582106, ExAC 0.08%). This variant has been observed in several individuals affected with myoadenylate deaminase deficiency (PMID: 12117480, 27296017). This variant is also known as Gln156His in the literature. ClinVar contains an entry for this variant (Variation ID: 197620). This variant has been reported to affect AMPD1 protein function (PMID: 12117480). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

From Centre for Mendelian Genomics,University Medical Centre Ljubljana, SCV001366486.2

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

Description

This variant was classified as: Likely pathogenic. The following ACMG criteria were applied in classifying this variant: PS3,PS4_MOD,PM2.

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

Last Updated: Jul 10, 2021

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