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NM_000488.4(SERPINC1):c.1057C>T (p.Pro353Ser) AND Hereditary antithrombin deficiency

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 29, 2020
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:
RCV001377779.2

Allele description [Variation Report for NM_000488.4(SERPINC1):c.1057C>T (p.Pro353Ser)]

NM_000488.4(SERPINC1):c.1057C>T (p.Pro353Ser)

Gene:
SERPINC1:serpin family C member 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1q25.1
Genomic location:
Preferred name:
NM_000488.4(SERPINC1):c.1057C>T (p.Pro353Ser)
HGVS:
  • NC_000001.11:g.173909648G>A
  • NG_012462.1:g.12731C>T
  • NM_000488.4:c.1057C>TMANE SELECT
  • NM_001365052.2:c.913C>T
  • NM_001386302.1:c.1180C>T
  • NM_001386303.1:c.1138C>T
  • NM_001386304.1:c.1036C>T
  • NM_001386305.1:c.1000C>T
  • NM_001386306.1:c.841C>T
  • NP_000479.1:p.Pro353Ser
  • NP_001351981.1:p.Pro305Ser
  • NP_001373231.1:p.Pro394Ser
  • NP_001373232.1:p.Pro380Ser
  • NP_001373233.1:p.Pro346Ser
  • NP_001373234.1:p.Pro334Ser
  • NP_001373235.1:p.Pro281Ser
  • LRG_577:g.12731C>T
  • NC_000001.10:g.173878786G>A
Protein change:
P281S
Links:
dbSNP: rs2102782517
NCBI 1000 Genomes Browser:
rs2102782517
Molecular consequence:
  • NM_000488.4:c.1057C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001365052.2:c.913C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386302.1:c.1180C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386303.1:c.1138C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386304.1:c.1036C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386305.1:c.1000C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001386306.1:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hereditary antithrombin deficiency (AT3D)
Synonyms:
Antithrombin III deficiency; Thrombophilia due to antithrombin III deficiency; Reduced antithrombin III activity; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0013144; MedGen: C0272375; OMIM: 613118; Human Phenotype Ontology: HP:0001976

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001575202Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 29, 2020) 		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

Identification of six novel mutations in type I antithrombin deficient Italian families.

Di Perna P, Vecchione G, D'Andrea G, Scenna G, Brancaccio V, Margaglione M.

Haematologica. 2004 Jan;89(1):117-8. No abstract available.

PubMed [citation]
PMID:
14754620

Clinical and laboratory characteristics of antithrombin deficiencies: A large cohort study from a single diagnostic center.

Gindele R, Selmeczi A, Oláh Z, Ilonczai P, Pfliegler G, Marján E, Nemes L, Nagy Á, Losonczy H, Mitic G, Kovac M, Balogh G, Komáromi I, Schlammadinger Á, Rázsó K, Boda Z, Muszbek L, Bereczky Z.

Thromb Res. 2017 Dec;160:119-128. doi: 10.1016/j.thromres.2017.10.023. Epub 2017 Oct 31.

PubMed [citation]
PMID:
29153735
See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001575202.1

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

Description

This sequence change replaces proline with serine at codon 353 of the SERPINC1 protein (p.Pro353Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with antithrombin deficiency (PMID: 14754620, 29153735). This variant is also known as Pro321Ser in the literature. 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.Pro353 amino acid residue in SERPINC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 25522812, 21264449, 24162787 25522812). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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

Last Updated: Oct 8, 2024