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NM_000312.4(PROC):c.1277G>A (p.Cys426Tyr) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jan 20, 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:
RCV003123381.3

Allele description [Variation Report for NM_000312.4(PROC):c.1277G>A (p.Cys426Tyr)]

NM_000312.4(PROC):c.1277G>A (p.Cys426Tyr)

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.1277G>A (p.Cys426Tyr)
HGVS:
  • NC_000002.12:g.127428837G>A
  • NG_016323.1:g.15418G>A
  • NM_000312.4:c.1277G>AMANE SELECT
  • NM_001375602.1:c.1460G>A
  • NM_001375603.1:c.1442G>A
  • NM_001375604.1:c.1340G>A
  • NM_001375605.1:c.1379G>A
  • NM_001375606.1:c.1445G>A
  • NM_001375607.1:c.1463G>A
  • NM_001375608.1:c.1220G>A
  • NM_001375609.1:c.1253G>A
  • NM_001375610.1:c.1271G>A
  • NM_001375611.1:c.1277G>A
  • NM_001375613.1:c.1277G>A
  • NP_000303.1:p.Cys426Tyr
  • NP_000303.1:p.Cys426Tyr
  • NP_001362531.1:p.Cys487Tyr
  • NP_001362532.1:p.Cys481Tyr
  • NP_001362533.1:p.Cys447Tyr
  • NP_001362534.1:p.Cys460Tyr
  • NP_001362535.1:p.Cys482Tyr
  • NP_001362536.1:p.Cys488Tyr
  • NP_001362537.1:p.Cys407Tyr
  • NP_001362538.1:p.Cys418Tyr
  • NP_001362539.1:p.Cys424Tyr
  • NP_001362540.1:p.Cys426Tyr
  • NP_001362542.1:p.Cys426Tyr
  • LRG_599t1:c.1277G>A
  • LRG_599:g.15418G>A
  • LRG_599p1:p.Cys426Tyr
  • NC_000002.11:g.128186413G>A
  • NM_000312.3:c.1277G>A
Protein change:
C407Y
Molecular consequence:
  • NM_000312.4:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375602.1:c.1460G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375603.1:c.1442G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375604.1:c.1340G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375605.1:c.1379G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375606.1:c.1445G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375607.1:c.1463G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375608.1:c.1220G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375609.1:c.1253G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375610.1:c.1271G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375611.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001375613.1:c.1277G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003800719Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(Jan 20, 2023) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Genetic mutations in ten unrelated American patients with symptomatic type 1 protein C deficiency.

Tsay W, Greengard JS, Montgomery RR, McPherson RA, Fucci JC, Koerper MA, Coughlin J, Griffin JH.

Blood Coagul Fibrinolysis. 1993 Oct;4(5):791-6.

PubMed [citation]
PMID:
8292730

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003800719.2

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

Description

Variant summary: PROC c.1277G>A (p.Cys426Tyr) results in a non-conservative amino acid change located in the Serine proteases, trypsin domain (IPR001254) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249544 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1277G>A has been reported in the literature in at-least one individual affected with Protein C Deficiency Type 1, Autosomal Dominant (example: Tsay_1993). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Nov 11, 2023