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NM_000313.4(PROS1):c.557G>A (p.Cys186Tyr) AND Thrombophilia due to protein S deficiency, autosomal recessive

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 24, 2022
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:
RCV001984812.6

Allele description [Variation Report for NM_000313.4(PROS1):c.557G>A (p.Cys186Tyr)]

NM_000313.4(PROS1):c.557G>A (p.Cys186Tyr)

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.557G>A (p.Cys186Tyr)
HGVS:
  • NC_000003.12:g.93905828C>T
  • NG_009813.1:g.73263G>A
  • NM_000313.4:c.557G>AMANE SELECT
  • NM_001314077.2:c.653G>A
  • NP_000304.2:p.Cys186Tyr
  • NP_001301006.1:p.Cys218Tyr
  • LRG_572:g.73263G>A
  • NC_000003.11:g.93624672C>T
Protein change:
C186Y
Links:
dbSNP: rs779391826
NCBI 1000 Genomes Browser:
rs779391826
Molecular consequence:
  • NM_000313.4:c.557G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001314077.2:c.653G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002213829Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 24, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Molecular basis of protein S deficiency in three families also showing independent inheritance of factor V leiden.

Beauchamp NJ, Daly ME, Cooper PC, Makris M, Preston FE, Peake IR.

Blood. 1996 Sep 1;88(5):1700-7.

PubMed [citation]
PMID:
8781426

Identification of 19 protein S gene mutations in patients with phenotypic protein S deficiency and thrombosis. Protein S Study Group.

Simmonds RE, Ireland H, Kunz G, Lane DA.

Blood. 1996 Dec 1;88(11):4195-204.

PubMed [citation]
PMID:
8943854
See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002213829.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (7)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PROS1 protein function. ClinVar contains an entry for this variant (Variation ID: 1435151). This variant is also known as p.Cys145Tyr. This missense change has been observed in individuals with protein S deficiency (PMID: 8781426, 8943854, 10706858, 20880255, 22261441, 28607330). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs779391826, gnomAD 0.0009%). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 186 of the PROS1 protein (p.Cys186Tyr).

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

Last Updated: Sep 29, 2024