NM_000313.4(PROS1):c.1998T>A (p.Cys666Ter) AND Thrombophilia due to protein S deficiency, autosomal recessive

This record was updated by the submitter. Please see the current version.

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 14, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000688177.3

Allele description

NM_000313.4(PROS1):c.1998T>A (p.Cys666Ter)

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.1998T>A (p.Cys666Ter)

HGVS:

NC_000003.12:g.93874278A>T
NG_009813.1:g.104813T>A
NM_000313.4:c.1998T>AMANE SELECT
NM_001314077.2:c.2094T>A
NP_000304.2:p.Cys666Ter
NP_000304.2:p.Cys666Ter
NP_001301006.1:p.Cys698Ter
LRG_572t1:c.1998T>A
LRG_572:g.104813T>A
LRG_572p1:p.Cys666Ter
NC_000003.11:g.93593122A>T
NM_000313.3:c.1998T>A

Protein change:

C666*

Links:

dbSNP: rs1559926604

NCBI 1000 Genomes Browser:

rs1559926604

Molecular consequence:

NM_000313.4:c.1998T>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001314077.2:c.2094T>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Thrombophilia due to protein S deficiency, autosomal recessive (THPH6)
Identifiers:: MONDO: MONDO:0013791; MedGen: C3281092; Orphanet: 743; OMIM: 614514

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000815779	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 14, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20181378, 29748776, 30669159, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815779

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 14, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Analysis three abnormal Protein S genes in a patient with pulmonary embolism.

Ikejiri M, Tsuji A, Wada H, Sakamoto Y, Nishioka J, Ota S, Yamada N, Matsumoto T, Nakatani K, Nobori T, Itoh M.

Thromb Res. 2010 Jun;125(6):529-32. doi: 10.1016/j.thromres.2009.12.025. Epub 2010 Feb 23.

PubMed [citation]

PMID:: 20181378

Distinctive regional-specific PROS1 mutation spectrum in Southern China.

Chan NCN, Cheng CK, Chan KCF, Wong CML, Lau KM, Kwong JHY, Chan NPH, Wong WS, Chow EYD, Wong MLG, Chu RW, Ip RKL, Ng MHL.

J Thromb Thrombolysis. 2018 Jul;46(1):120-124. doi: 10.1007/s11239-018-1660-z. No abstract available.

PubMed [citation]

PMID:: 29748776

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV000815779.3

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

Description

This sequence change creates a premature translational stop signal (p.Cys666*) in the PROS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the PROS1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PROS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 567962). This variant disrupts a region of the PROS1 protein in which other variant(s) (p.Pro667Leu) have been determined to be pathogenic (PMID: 20181378, 29748776, 30669159; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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

Last Updated: Feb 20, 2024

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