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

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: May 1, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV000443069.19

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:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000343429	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 9, 2017)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 11474657, 18515255, 19437508, 19654085, 22723858, 10234508, 27296815 Citation Link,
SCV000516540	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Feb 14, 2023)	germline	clinical testing	Citation Link,
SCV004130295	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (May 1, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000343429

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL Classification Definitions 2015)

Pathogenic
(Aug 9, 2017)

germline

clinical testing

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

Citation Link,

SCV000516540

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Feb 14, 2023)

germline

clinical testing

Citation Link,

SCV004130295

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(May 1, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	4	not provided	not provided	not provided	not provided	clinical 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 Eurofins Ntd Llc (ga), SCV000343429.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	not provided	not provided	clinical testing	PubMed (7)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		4	not provided	not provided	not provided

From GeneDx, SCV000516540.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Published functional studies demonstrate reduced alpha-1-antitrypsin secretion and a complete intracellular transport block (Fra et al., 2012; Poller et al., 1999); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as P369S or Mwurzburg allele using alternate nomenclature; This variant is associated with the following publications: (PMID: 31980526, 10234508, 27296815, 11474657, 31447099, 34426522, 22723858, 31661293, 21228398, 29882371)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CeGaT Center for Human Genetics Tuebingen, SCV004130295.10

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	not provided	not provided	clinical testing	not provided

Description

SERPINA1: PM3:Strong, PM1, PM2, PM5, PP4:Moderate, PS3:Supporting

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		3	not provided	not provided	not provided

Last Updated: Oct 20, 2024

ClinVar

Relating variation to medicine