NM_000488.4(SERPINC1):c.1395A>C (p.Ter465Tyr) AND Hereditary antithrombin deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 4, 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:: RCV002975940.3

Allele description [Variation Report for NM_000488.4(SERPINC1):c.1395A>C (p.Ter465Tyr)]

NM_000488.4(SERPINC1):c.1395A>C (p.Ter465Tyr)

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.1395A>C (p.Ter465Tyr)

HGVS:

NC_000001.11:g.173903889T>G
NG_012462.1:g.18490A>C
NM_000488.4:c.1395A>CMANE SELECT
NM_001365052.2:c.1251A>C
NM_001386302.1:c.1518A>C
NM_001386303.1:c.1476A>C
NM_001386304.1:c.1374A>C
NM_001386305.1:c.1338A>C
NM_001386306.1:c.1179A>C
NP_000479.1:p.Ter465Tyr
NP_000479.1:p.Ter465Tyr
NP_001351981.1:p.Ter417Tyr
NP_001373231.1:p.Ter506Tyr
NP_001373232.1:p.Ter492Tyr
NP_001373233.1:p.Ter458Tyr
NP_001373234.1:p.Ter446Tyr
NP_001373235.1:p.Ter393Tyr
LRG_577t1:c.1395A>C
LRG_577:g.18490A>C
LRG_577p1:p.Ter465Tyr
NC_000001.10:g.173873027T>G
NM_000488.3:c.1395A>C

Molecular consequence:

NM_000488.4:c.1395A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001365052.2:c.1251A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386302.1:c.1518A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386303.1:c.1476A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386304.1:c.1374A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386305.1:c.1338A>C - stop lost - [Sequence Ontology: SO:0001578]
NM_001386306.1:c.1179A>C - stop lost - [Sequence Ontology: SO:0001578]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003286328	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 4, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 22398878, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003286328

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 4, 2022)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

Molecular analysis and genotype-phenotype correlation in patients with antithrombin deficiency from Southern Italy.

Castaldo G, Cerbone AM, Guida A, Tandurella I, Ingino R, Tufano A, Ceglia C, Di Minno MN, Ruocco AL, Di Minno G.

Thromb Haemost. 2012 Apr;107(4):673-80. doi: 10.1160/TH11-09-0671. Epub 2012 Mar 8.

PubMed [citation]

PMID:: 22398878

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003286328.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant is not present in population databases (gnomAD no frequency). 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. This variant results in an extension of the SERPINC1 protein. Other variant(s) that result in a similarly extended protein product (c.1394A>C (p.*465Serext*28)) have been observed in individuals with SERPINC1-related disease (PMID: 22398878). This suggests that these extensions may be clinically significant. This protein extension has been observed in individual(s) with clinical features of antithrombin III deficiency (Invitae). This sequence change disrupts the translational stop signal of the SERPINC1 mRNA. It is expected to extend the length of the SERPINC1 protein by an uncertain number of additional amino acid residues.

#	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: Oct 8, 2024

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