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NM_000313.4(PROS1):c.1919T>C (p.Met640Thr) AND Thrombophilia due to protein S deficiency, autosomal recessive

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 7, 2019
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:
RCV001211450.5

Allele description [Variation Report for NM_000313.4(PROS1):c.1919T>C (p.Met640Thr)]

NM_000313.4(PROS1):c.1919T>C (p.Met640Thr)

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.1919T>C (p.Met640Thr)
HGVS:
  • NC_000003.12:g.93874357A>G
  • NG_009813.1:g.104734T>C
  • NM_000313.4:c.1919T>CMANE SELECT
  • NM_001314077.2:c.2015T>C
  • NP_000304.2:p.Met640Thr
  • NP_001301006.1:p.Met672Thr
  • LRG_572t1:c.1919T>C
  • LRG_572:g.104734T>C
  • NC_000003.11:g.93593201A>G
  • NM_000313.3:c.1919T>C
Protein change:
M640T
Links:
dbSNP: rs1708152510
NCBI 1000 Genomes Browser:
rs1708152510
Molecular consequence:
  • NM_000313.4:c.1919T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001314077.2:c.2015T>C - 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
SCV001382991Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 7, 2019) 		germlineclinical testing

PubMed (5)
[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

Visual fields measured with double-arc perimetry in eyes with threshold retinopathy of prematurity from the cryotherapy for retinopathy of prematurity trial. The CRYO-Retinopathy of Prematurity Cooperative Group.

Quinn GE, Dobson V, Hardy RJ, Tung B, Phelps DL, Palmer EA.

Ophthalmology. 1996 Sep;103(9):1432-7.

PubMed [citation]
PMID:
8841302

Functional characterization of twelve natural PROS1 mutations associated with anticoagulant protein S deficiency.

Hurtado B, Muñoz X, Mulero MC, Navarro G, Domènech P, García de Frutos P, Pérez-Riba M, Sala N.

Haematologica. 2008 Apr;93(4):574-80. doi: 10.3324/haematol.12090. Epub 2008 Mar 5.

PubMed [citation]
PMID:
18322254
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001382991.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces methionine with threonine at codon 640 of the PROS1 protein (p.Met640Thr). The methionine residue is highly conserved and there is a moderate physicochemical difference between methionine and threonine. For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met640 amino acid residue in PROS1. Other variant(s) that disrupt this residue have been observed in individuals with PROS1-related conditions (PMID: 8841302), which suggests that this may be a clinically significant amino acid residue. This variant has been reported to affect PROS1 protein function (PMID: 18322254). This variant has been observed to segregate with protein S deficiency in families (PMID: 10790208, 18435454). This variant is also known as M599T in the literature. This variant is not present in population databases (ExAC no frequency).

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

Last Updated: Sep 29, 2024