NM_000312.4(PROC):c.160A>T (p.Ser54Cys) AND Thrombophilia due to protein C deficiency, autosomal dominant

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Jan 16, 2024
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:: RCV000148744.10

Allele description [Variation Report for NM_000312.4(PROC):c.160A>T (p.Ser54Cys)]

NM_000312.4(PROC):c.160A>T (p.Ser54Cys)

Gene:

PROC:protein C, inactivator of coagulation factors Va and VIIIa [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q14.3

Genomic location:

Preferred name:

NM_000312.4(PROC):c.160A>T (p.Ser54Cys)

Other names:

p.Ser54Cys

HGVS:

NC_000002.12:g.127421372A>T
NG_016323.1:g.7953A>T
NM_000312.4:c.160A>TMANE SELECT
NM_001375602.1:c.343A>T
NM_001375603.1:c.223A>T
NM_001375604.1:c.223A>T
NM_001375605.1:c.160A>T
NM_001375606.1:c.223A>T
NM_001375607.1:c.244A>T
NM_001375608.1:c.160A>T
NM_001375609.1:c.136A>T
NM_001375610.1:c.154A>T
NM_001375611.1:c.160A>T
NM_001375613.1:c.160A>T
NP_000303.1:p.Ser54Cys
NP_000303.1:p.Ser54Cys
NP_001362531.1:p.Ser115Cys
NP_001362532.1:p.Ser75Cys
NP_001362533.1:p.Ser75Cys
NP_001362534.1:p.Ser54Cys
NP_001362535.1:p.Ser75Cys
NP_001362536.1:p.Ser82Cys
NP_001362537.1:p.Ser54Cys
NP_001362538.1:p.Ser46Cys
NP_001362539.1:p.Ser52Cys
NP_001362540.1:p.Ser54Cys
NP_001362542.1:p.Ser54Cys
LRG_599t1:c.160A>T
LRG_599:g.7953A>T
LRG_599p1:p.Ser54Cys
NC_000002.11:g.128178948A>T
NM_000312.3:c.160A>T

Protein change:

S115C

Links:

dbSNP: rs376049280

NCBI 1000 Genomes Browser:

rs376049280

Molecular consequence:

NM_000312.4:c.160A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375602.1:c.343A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375603.1:c.223A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375604.1:c.223A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375605.1:c.160A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375606.1:c.223A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375607.1:c.244A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375608.1:c.160A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375609.1:c.136A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375610.1:c.154A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375611.1:c.160A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001375613.1:c.160A>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Thrombophilia due to protein C deficiency, autosomal dominant
Synonyms:: PROC DEFICIENCY, AUTOSOMAL DOMINANT; PROTEIN C DEFICIENCY, AUTOSOMAL DOMINANT; Thrombophilia, hereditary, due to protein C deficiency, autosomal dominant
Identifiers:: MONDO: MONDO:0008316; MedGen: C2674321; Orphanet: 745; OMIM: 176860

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000190481	CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation	no assertion criteria provided	Uncertain significance (Jun 1, 2014)	germline	research
SCV000956445	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 16, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 7482420, 7740502, 7795150, 10669160, 31821907, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000190481

CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation

no assertion criteria provided

Uncertain significance
(Jun 1, 2014)

germline

research

SCV000956445

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 16, 2024)

germline

clinical testing

PubMed (6)
[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, research

Citations

PubMed

Protein C deficiency: a database of mutations, 1995 update. On behalf of the Subcommittee on Plasma Coagulation Inhibitors of the Scientific and Standardization Committee of the ISTH.

Reitsma PH, Bernardi F, Doig RG, Gandrille S, Greengard JS, Ireland H, Krawczak M, Lind B, Long GL, Poort SR, et al.

Thromb Haemost. 1995 May;73(5):876-89. Review. No abstract available.

PubMed [citation]

PMID:: 7482420

Prevalence of protein C deficiency in the healthy population.

Tait RC, Walker ID, Reitsma PH, Islam SI, McCall F, Poort SR, Conkie JA, Bertina RM.

Thromb Haemost. 1995 Jan;73(1):87-93.

PubMed [citation]

PMID:: 7740502

See all PubMed Citations (6)

Details of each submission

From CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation, SCV000190481.1

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

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000956445.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 54 of the PROC protein (p.Ser54Cys). This variant is present in population databases (rs376049280, gnomAD 0.01%). This missense change has been observed in individual(s) with PROC related conditions (PMID: 7482420, 7740502, 7795150, 10669160, 31821907). ClinVar contains an entry for this variant (Variation ID: 161338). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain 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

Last Updated: Sep 29, 2024

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