NM_000488.4(SERPINC1):c.551T>C (p.Leu184Pro) AND Hereditary antithrombin deficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 28, 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:: RCV003526265.1

Allele description

NM_000488.4(SERPINC1):c.551T>C (p.Leu184Pro)

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.551T>C (p.Leu184Pro)

HGVS:

NC_000001.11:g.173911872A>G
NG_012462.1:g.10507T>C
NM_000488.4:c.551T>CMANE SELECT
NM_001365052.2:c.407T>C
NM_001386302.1:c.551T>C
NM_001386303.1:c.632T>C
NM_001386304.1:c.551T>C
NM_001386305.1:c.551T>C
NM_001386306.1:c.409-981T>C
NP_000479.1:p.Leu184Pro
NP_000479.1:p.Leu184Pro
NP_001351981.1:p.Leu136Pro
NP_001373231.1:p.Leu184Pro
NP_001373232.1:p.Leu211Pro
NP_001373233.1:p.Leu184Pro
NP_001373234.1:p.Leu184Pro
LRG_577t1:c.551T>C
LRG_577:g.10507T>C
LRG_577p1:p.Leu184Pro
NC_000001.10:g.173881010A>G
NM_000488.3:c.551T>C

Protein change:

L136P

Molecular consequence:

NM_001386306.1:c.409-981T>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000488.4:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001365052.2:c.407T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386302.1:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386303.1:c.632T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386304.1:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001386305.1:c.551T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hereditary antithrombin deficiency
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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Uncultured Prevotellaceae bacterium isolate RUG062, whole genome shotgun sequenc...
Uncultured Prevotellaceae bacterium isolate RUG062, whole genome shotgun sequencing project
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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004320477	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 28, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28300866, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004320477

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 28, 2023)

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

Thrombotic risk according to SERPINC1 genotype in a large cohort of subjects with antithrombin inherited deficiency.

Alhenc-Gelas M, Plu-Bureau G, Hugon-Rodin J, Picard V, Horellou MH; GFHT study group on Genetic Thrombophilia..

Thromb Haemost. 2017 Jun 2;117(6):1040-1051. doi: 10.1160/TH16-08-0635. Epub 2017 Mar 16.

PubMed [citation]

PMID:: 28300866

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 Invitae, SCV004320477.1

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

Description

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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt SERPINC1 protein function. This missense change has been observed in individual(s) with autosomal dominant antithrombin III deficiency (PMID: 28300866). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 184 of the SERPINC1 protein (p.Leu184Pro).

#	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: Feb 20, 2024

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