NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro) AND Thrombophilia due to protein S deficiency, autosomal dominant

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Nov 21, 2018
Review status:: criteria provided, conflicting classifications

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:: RCV000755688.11

Allele description [Variation Report for NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro)]

NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro)

Gene:

PROS1:protein S [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q11.1

Genomic location:

Preferred name:

NM_000313.4(PROS1):c.1501T>C (p.Ser501Pro)

Other names:

S460P

HGVS:

NC_000003.12:g.93879306A>G
NG_009813.1:g.99785T>C
NM_000313.4:c.1501T>CMANE SELECT
NM_001314077.2:c.1597T>C
NP_000304.2:p.Ser501Pro
NP_000304.2:p.Ser501Pro
NP_001301006.1:p.Ser533Pro
LRG_572t1:c.1501T>C
LRG_572:g.99785T>C
LRG_572p1:p.Ser501Pro
NC_000003.11:g.93598150A>G
NM_000313.3:c.1501T>C
P07225:p.Ser501Pro

Protein change:

S501P; SER460PRO

Links:

UniProtKB: P07225#VAR_005568; OMIM: 176880.0001; dbSNP: rs121918472

NCBI 1000 Genomes Browser:

rs121918472

Molecular consequence:

NM_000313.4:c.1501T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001314077.2:c.1597T>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Thrombophilia due to protein S deficiency, autosomal dominant (THPH5)
Identifiers:: MONDO: MONDO:0012868; MedGen: C3278211; Orphanet: 743; OMIM: 612336

Recent activity

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Sulfur-oxidizing endosymbiont of Gigantopelta aegis strain Gae_SOB, whole genome...
Sulfur-oxidizing endosymbiont of Gigantopelta aegis strain Gae_SOB, whole genome shotgun sequencing project
gi|1945544587|gb|JAEHGE000000000.1| E010000000

Nucleotide
acyl-CoA wax alcohol acyltransferase 1 [Homo sapiens]
acyl-CoA wax alcohol acyltransferase 1 [Homo sapiens]
gi|61888902|ref|NP_001013597.1|

Protein
F-box only protein 5 isoform X2 [Cygnus olor]
F-box only protein 5 isoform X2 [Cygnus olor]
gi|2022854635|ref|XP_040407303.1|

Protein
PREDICTED: Papio anubis beta-transducin repeat containing E3 ubiquitin protein l...
PREDICTED: Papio anubis beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), transcript variant X1, mRNA
gi|1777256985|ref|XM_017944244.3|

Nucleotide
lysine-specific demethylase 2B isoform X1 [Choloepus didactylus]
lysine-specific demethylase 2B isoform X1 [Choloepus didactylus]
gi|1934723099|ref|XP_037672467.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000883101	Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 21, 2018)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001306866	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Feb 16, 2018)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 28374852, 18841302, 28607330, 21764424, 22273984, 7579448, 2143091, 15175796 Citation Link,
SCV002500909	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004041785	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Uncertain significance (Oct 9, 2023)	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	2	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Protein S Heerlen mutation heterozygosity is associated with venous thrombosis risk.

Suchon P, Germain M, Delluc A, Smadja D, Jouven X, Gyorgy B, Saut N, Ibrahim M, Deleuze JF, Alessi MC, Morange PE, Trégouët DA.

Sci Rep. 2017 Apr 4;7:45507. doi: 10.1038/srep45507.

PubMed [citation]

PMID:: 28374852
PMCID:: PMC5379621

Confirmation of inherited protein S deficiency by PROS1 mutational screening: Identification of three novel PROS1 mutations and haplotype analysis of p.Q279X recurrence.

Hurtado B, Abasolo N, Domènech-Santasusana P, Fuentes-Prior P, García de Frutos P, Sala N.

Thromb Haemost. 2008 Oct;100(4):721-4. No abstract available.

PubMed [citation]

PMID:: 18841302

See all PubMed Citations (9)

Details of each submission

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000883101.1

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

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

From Illumina Laboratory Services, Illumina, SCV001306866.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (8)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	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		not provided	not provided	not provided	not provided

From ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV002500909.2

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

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

From Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004041785.1

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

#	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

Last Updated: Oct 13, 2024

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