Rs17602729

Orientation

minus

is a	snp
is	mentioned by
dbSNP	rs17602729
PheGenI	rs17602729
nextbio	rs17602729
hapmap	rs17602729
1000 genomes	rs17602729
hgdp	rs17602729
ensembl	rs17602729
gopubmed	rs17602729
geneview	rs17602729
scholar	rs17602729
google	rs17602729
pharmgkb	rs17602729
gwascentral	rs17602729
openSNP	rs17602729
23andMe	rs17602729
23andMe all	rs17602729
SNP Nexus
SNPshot	rs17602729
SNPdbe	rs17602729
MSV3d	rs17602729

Gene

AMPD1

Chromosome

1

Orientation

minus

Position

115236057

Reference

GRCh37 37.1/131

Max Magnitude

4

Geno	Mag	Summary
(A;A)	4	AMPD1 deficiency homozygous (orientation reversed)
(A;C)	2.1	unexpected genotype
(A;G)	3	AMPD1 deficiency heterozygous (orientation reversed)
(A;T)	3.5	Really unexpected!
(C;C)	0	normal
(C;G)	2.1	unexpected genotype
(C;T)	3	AMPD1 deficiency heterozygous
(G;G)	0	normal (orientation reversed)
(G;T)	3.4	unexpected genotype
(T;T)	4	AMPD1 deficiency homozygous

?	(C;C) (C;T) (T;T)	28

This position is odd. Under the older build36, it was on the plus strand, as of build37 it is now on the minus strand. This makes is very prone to some ambiguous flip confusion in ther literature, plus 23andMe users self reporting the flipped form. Instead of the usual bi-allelic SNP, all 4 alleles are reported in dbSNP, however this is probably due to the strand changes. dbSNP currently says the normal 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 16505069]

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]

OMIM	102770
Desc	AMPD DEFICIENCY
Variant	0001
Related	also

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

ClinVar
Risk	rs17602729(A,G,T;A,G,T)
Normal	rs17602729(C;C)
Significance	5
Disease	Muscle AMP deaminase deficiency
ClinVar	info
Gene	AMPD1
CLNDBN	Muscle AMP deaminase deficiency
Reversed	1
CLNHGVS	NC_000001.10:g.115236057G>A
CLNSRC	OMIM Allelic Variant

[PMID 18852891] Distribution and effects of nonsense polymorphisms in human genes.

[PMID 18974781] Cataloging coding sequence variations in human genome databases.

[PMID 19237423] Is there an optimum endurance polygenic profile?

GET Evidence
AMPD1-Q12X
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