NM_000313.4(PROS1):c.1063C>T (p.Arg355Cys) AND Thrombophilia due to protein S deficiency, autosomal recessive

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 23, 2021
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:: RCV001232043.5

Allele description [Variation Report for NM_000313.4(PROS1):c.1063C>T (p.Arg355Cys)]

NM_000313.4(PROS1):c.1063C>T (p.Arg355Cys)

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.1063C>T (p.Arg355Cys)

HGVS:

NC_000003.12:g.93893025G>A
NG_009813.1:g.86066C>T
NM_000313.4:c.1063C>TMANE SELECT
NM_001314077.2:c.1159C>T
NP_000304.2:p.Arg355Cys
NP_000304.2:p.Arg355Cys
NP_001301006.1:p.Arg387Cys
LRG_572t1:c.1063C>T
LRG_572:g.86066C>T
LRG_572p1:p.Arg355Cys
NC_000003.11:g.93611869G>A
NM_000313.3:c.1063C>T

Protein change:

R355C; ARG355CYS

Links:

OMIM: 176880.0009; dbSNP: rs387906674

NCBI 1000 Genomes Browser:

rs387906674

Molecular consequence:

NM_000313.4:c.1063C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001314077.2:c.1159C>T - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001404587	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 23, 2021)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 29748776, 21764702, 27667277, 21172841, 21486865, 27748013, 15238143, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001404587

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 23, 2021)

germline

clinical testing

PubMed (8)
[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

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

[Recurrent deep vein thrombosis caused by heterozygous missense mutation of the protein S gene: genetic analysis of a case].

Ye X, Liu XL, Feng Y, Zhou XH, Xing ZF.

Nan Fang Yi Ke Da Xue Xue Bao. 2011 Jun;31(7):1228-31. Chinese.

PubMed [citation]

PMID:: 21764702

See all PubMed Citations (8)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001404587.4

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

Description

This variant is present in population databases (rs387906674, ExAC 0.05%). This sequence change replaces arginine with cysteine at codon 355 of the PROS1 protein (p.Arg355Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant has been observed in individual(s) with protein S deficiency (PMID: 29748776, 21764702, 27667277, 21172841, 21486865, 27748013). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Arg314Cys in the literature. ClinVar contains an entry for this variant (Variation ID: 29846). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Arg355 amino acid residue in PROS1. Other variant(s) that disrupt this residue have been observed in individuals with PROS1-related conditions (PMID: 15238143), which suggests that this may be a clinically significant amino acid residue. 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: Sep 29, 2024

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