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From SNPedia

Geno Mag Summary
(A;A) 3 AMPD1 deficiency homozygous (orientation reversed)
(A;C) 2.1 unexpected genotype
(A;G) 2.8 AMPD1 deficiency heterozygous (orientation reversed)
(A;T) 3.5 Really unexpected!
(C;C) 0 normal
(C;G) 2.1 unexpected genotype
(C;T) 2.8 AMPD1 deficiency heterozygous
(G;G) 0 normal (orientation reversed)
(G;T) 3.4 unexpected genotype
(T;T) 3 AMPD1 deficiency homozygous
ReferenceGRCh38 38.1/141
is asnp
is mentioned by
1000 genomesrs17602729
23andMe allrs17602729
SNP Nexus

GWAS Ctlgrs17602729
Max Magnitude3.5
? (C;C) (C;T) (T;T) 28
This position is odd. Under the older reference genome build36, it was on the plus strand; in build37 it is on the minus strand. This makes it very prone to some ambiguous flip confusion in the literature, plus, 23andMe users have self-reported the flipped form. IN addition, instead of the usual SNP listed as having 2 alleles, all 4 alleles are reported in dbSNP, even if this is probably due to the strand changes. dbSNP currently says the normal allele is C, and T is the rare geno which causes a premature stop, early in the gene. We at SNPedia suspect that the A & G alleles are not common enough to have ever been genuinely reported, but for de-novo mutations each allele would be non-synonymous and result in a different amino acid. http://snpedia.blogspot.com/2012/12/snpedias-nightmare-before-christmas.html

rs17602729, a SNP located in the AMPD1 gene and also known as 'C34T', has at times been called the "most prevalent genetic disease mutation", at least in Caucasians. [PMID 11331279] Perhaps up to 10% of Caucasians and African-American carry one C34T allele (i.e. carry one rs17602729(A) allele) - and actually, most of them are unaware of any medically related issues since they don't typically have any particular symptoms that would warrant a trip to the doctor.

So what's the issue? The AMPD1 gene encodes the enzyme adenosine monophosphate deaminase, which is one of the key enzymes used to process the energy source ATP. The C34T variation causes a premature stop in the protein, leading to a nonfunctional AMPD1 enzyme. Some individuals - but by no means all or even a majority apparently - who are AMPD1 deficient get muscle cramps and pains when they exert themselves. The most common genotype bringing this about is rs17602729(A;A), i.e. the individuals who carry two copies of the C34T allele and therefore have no functioning AMPD1 allele. It is not known why only some of C34T homozygotes experience muscle myalgia.

Heterozygotes, i.e. rs17602729(A;G) individuals, do not seem to suffer any exercise or fitness related deficit. In fact, one of the best elite Caucasian distance runners is known to be a C34T heterozygote. [PMID 16505069OA-icon.png]

In fact, heterozygotes for rs17602729 may even have advantages over those lacking a C34T allele. The most striking study reported that C34T heterozygotes are 8.6 fold (CI: 3.05 - 23.87) more likely to survive for more than 5 years without needing a heart transplant after a congestive heart failure related hospitalization than the wild-type homozygotes (i.e. rs17602729(G;G) homozygotes). [PMID 10086964] Similarly, C34T heterozygotes with coronary artery disease seem to fare better than wild-type homozygotes. [PMID 11028479]

This is one of the SNPs reported by NutraHacker.

[PMID 21211004OA-icon.png] Circulating adenosine increases during human experimental endotoxemia but blockade of its receptor does not influence the immune response and subsequent organ injury

Risk rs17602729(T;T)
Alt rs17602729(T;T)
Reference rs17602729(C;C)
Significance Pathogenic
Disease Muscle AMP deaminase deficiency
Variation info
Gene AMPD1
CLNDBN Muscle AMP deaminase deficiency
Reversed 1
HGVS NC_000001.11:g.114693436G>A
CLNSRC GTR OMIM Allelic Variant
CLNACC RCV000019933.28,

[PMID 18852891OA-icon.png] Distribution and effects of nonsense polymorphisms in human genes.

[PMID 18974781OA-icon.png] Cataloging coding sequence variations in human genome databases.

[PMID 19237423OA-icon.png] Is there an optimum endurance polygenic profile?

GET Evidence
aa_change Gln12Stop
aa_change_short Q12X
impact pathogenic
qualified_impact Low clinical importance, Likely pathogenic
overall_frequency 0.0930643
summary Causes Adenosine Deaminase Deficiency in a recessive manner. Most of the time individuals do not report symptoms, but when symptoms do exist they to be post-exercise symptoms of muscle weakness, muscle pain, and getting tired more quickly.

[PMID 23681449] Genes for Elite Power and Sprint Performance: ACTN3 Leads the Way

[PMID 25682119] Genetic Factors Associated with Exercise Performance in Atmospheric Hypoxia

[PMID 26529652] Effects of the 34C>T Variant of the AMPD1 Gene on Immune Function, Multi-Organ Dysfunction and Mortality in Sepsis Patients

[PMID 26554440] AMPD1 polymorphism and response to regadenoson