NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser) AND not provided

Clinical significance:Pathogenic (Last evaluated: Aug 9, 2017)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000443069.2

Allele description [Variation Report for NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)]

NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)

Gene:
SERPINA1:serpin family A member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.13
Genomic location:
Preferred name:
NM_000295.5(SERPINA1):c.1177C>T (p.Pro393Ser)
HGVS:
  • NC_000014.9:g.94378529G>A
  • NG_008290.1:g.17164C>T
  • NM_000295.5:c.1177C>TMANE SELECT
  • NM_001002235.3:c.1177C>T
  • NM_001002236.3:c.1177C>T
  • NM_001127700.2:c.1177C>T
  • NM_001127701.2:c.1177C>T
  • NM_001127702.2:c.1177C>T
  • NM_001127703.2:c.1177C>T
  • NM_001127704.2:c.1177C>T
  • NM_001127705.2:c.1177C>T
  • NM_001127706.2:c.1177C>T
  • NM_001127707.2:c.1177C>T
  • NP_000286.3:p.Pro393Ser
  • NP_001002235.1:p.Pro393Ser
  • NP_001002236.1:p.Pro393Ser
  • NP_001121172.1:p.Pro393Ser
  • NP_001121173.1:p.Pro393Ser
  • NP_001121173.1:p.Pro393Ser
  • NP_001121174.1:p.Pro393Ser
  • NP_001121175.1:p.Pro393Ser
  • NP_001121176.1:p.Pro393Ser
  • NP_001121177.1:p.Pro393Ser
  • NP_001121178.1:p.Pro393Ser
  • NP_001121179.1:p.Pro393Ser
  • LRG_575t1:c.1177C>T
  • LRG_575:g.17164C>T
  • LRG_575p1:p.Pro393Ser
  • NC_000014.8:g.94844866G>A
  • NM_000295.4:c.1177C>T
  • NM_001127701.1:c.1177C>T
Protein change:
P393S
Links:
dbSNP: rs61761869
NCBI 1000 Genomes Browser:
rs61761869
Molecular consequence:
  • NM_000295.5:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001002235.3:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001002236.3:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127700.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127701.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127702.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127703.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127704.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127705.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127706.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127707.2:c.1177C>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
4

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000343429EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Aug 9, 2017)
germlineclinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link,

SCV000516540GeneDxcriteria provided, single submitter
Pathogenic
(Mar 27, 2015)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown4not providednot providednot providednot providedclinical testing

Citations

PubMed

Association between the defective Pro369Ser mutation and in vivo intrahepatic 1-antitrypsin accumulation.

Seixas S, Lopes AI, Rocha J, Silva L, Salgueiro C, Salazar-de-Sousa J, Batista A.

J Med Genet. 2001 Jul;38(7):472-4. No abstract available.

PubMed [citation]
PMID:
11474657
PMCID:
PMC1757189

SERPINA1 gene variants in individuals from the general population with reduced alpha1-antitrypsin concentrations.

Zorzetto M, Russi E, Senn O, Imboden M, Ferrarotti I, Tinelli C, Campo I, Ottaviani S, Scabini R, von Eckardstein A, Berger W, Brändli O, Rochat T, Luisetti M, Probst-Hensch N; SAPALDIA Team..

Clin Chem. 2008 Aug;54(8):1331-8. doi: 10.1373/clinchem.2007.102798. Epub 2008 May 29.

PubMed [citation]
PMID:
18515255
See all PubMed Citations (7)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000343429.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided4not providednot providedclinical testing PubMed (7)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided4not providednot providednot provided

From GeneDx, SCV000516540.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The P393S variant in the SERPINA1 gene was first reported (reported as P369S and the Mwurzburg allele due to alternative nomenclature) in the heterozygous state in a patient with decreased serum alpha-1-antitrypsin levels but no evidence of lung or liver disease (Poller et al., 1999). It was later reported in a patient with cholestasis and intrahepatic alpha-1-antitrypsin accumulation who was a compound heterozygote for the P393S variant and an S variant allele (Seixas et al., 2001). The P393S substitution was not observed with a significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The P393S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species. Functional studies show that the P393S variant results in intracellular accumulation and reduced secretion of alpha1-antitrypsin (Poller et al., 1999; Fra et al., 2012). We interpret P393S as a pathogenic variant.

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

Last Updated: Jul 7, 2021

Support Center