AATVar : a database of human alpha-1 antitrypsin variants
Mmalton
Mutation sequence analysis
Contributed by
CHU Lille
HGVS nomenclature (NM_000295.4)
Usual nomenclature (Without signal peptide)
Nomenclarure including the signal peptide
c.227_229delTCT
Type of variation
AAT variant
Mutation Location
Exon 2
Genetic background
M2
ACMG classification
Pathogenic
Comments
The Pi Mmalton variant was first discovered by Cox in 1976.
AAT variant and Q0 alleles
Variant name
Mmalton
Also Known as
pathogenicity
Deficient Precipitating
HGVS nomenclature protéine
p.Phe76del
3D position of aa affecteded
Mobility on polyacrylamide gel
Mobility on agarose gel
M
AATserum level (g/L)
Heterozygous
0.69
Homozygous
0.12
Anti-elastolytic activity (IU/L)
Heterozygous
Homozygous
Comments
Slightly more cathodal mobility than M2 on IEF gels. At the heterozygous state, it thus may be confounded with an M protein.
Occurrence
Ethnic background without frequency range
Ethnic background and frequency
Frequency range
from (%)
To (%)
0.04
Group tested
Size
Description (who was tested)
Occurrence comments
from gnomAD (2.1).
However, the Pi Mmalton variant is not so rare in Spain, Sardinia and Maghreb countries.
Overall comments
Occurrence comments
This variant was identified at a homozygous status in a 47-year old man presenting with pulmonary emphysema. This variant was also identified at a homozygous status in a 48-year old man presenting with pulmonary emphysema and treated by substitution therapy (picture 2).
Some associations with the Pi Z allele have been described (see Ref. 2):
- a 41-year-old man of french caucasian origin with severe dyspnea (AAT = 0.33 g/L)
- a 37-year-old woman with asthma and bronchiectasis (AAT = 0.22 g/L)
References n°1
Medline ID
26446624
Authors
Joly P,Guillaud O,Hervieu V,Francina A,Mornex JF,Chapuis-Cellier C
Title
Clinical heterogeneity and potential high pathogenicity of the Mmalton Alpha 1 antitrypsin allele at the homozygous, compound heterozygous and heterozygous states.
