NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu) AND Hereditary antithrombin deficiency

Germline classification:: Pathogenic (19 submissions)
Last evaluated:: Sep 21, 2023
Review status:: 3 stars out of maximum of 4 stars
reviewed by expert panel

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:: RCV000019627.76

Allele description [Variation Report for NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu)]

NM_000488.4(SERPINC1):c.218C>T (p.Pro73Leu)

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.218C>T (p.Pro73Leu)

Other names:

P41L; NM_000488.3(SERPINC1):c.218C>T

HGVS:

NC_000001.11:g.173914743G>A
NG_012462.1:g.7636C>T
NM_000488.4:c.218C>TMANE SELECT
NM_001365052.2:c.74C>T
NM_001386302.1:c.218C>T
NM_001386303.1:c.299C>T
NM_001386304.1:c.218C>T
NM_001386305.1:c.218C>T
NM_001386306.1:c.218C>T
NP_000479.1:p.Pro73Leu
NP_000479.1:p.Pro73Leu
NP_001351981.1:p.Pro25Leu
NP_001373231.1:p.Pro73Leu
NP_001373232.1:p.Pro100Leu
NP_001373233.1:p.Pro73Leu
NP_001373234.1:p.Pro73Leu
NP_001373235.1:p.Pro73Leu
LRG_577t1:c.218C>T
LRG_577:g.7636C>T
LRG_577p1:p.Pro73Leu
NC_000001.10:g.173883881G>A
NM_000488.3:c.218C>T
P01008:p.Pro73Leu

Protein change:

P100L; PRO41LEU

Links:

UniProtKB: P01008#VAR_007036; OMIM: 107300.0012; dbSNP: rs121909551

Molecular consequence:

NM_000488.4:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001365052.2:c.74C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386302.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386303.1:c.299C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386304.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386305.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001386306.1:c.218C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000351487	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Pathogenic (Apr 27, 2017)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 23910795, 27322195, 3080419, 24956267, 2794060 Citation Link,
SCV000756581	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 1, 2026)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 23910795, 24956267, 26748602, 28317092, 2794060, 3080419, 24082793, 27322195, 28492532
SCV000899323	NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 1, 2019)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 25741868, 31064749
SCV001983481	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Sep 30, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 33614741, 27322195, 3080419, 22498748, 2794060, 23910795 Citation Link,
SCV002019179	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 21, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002515499	ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002810338	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 22, 2022)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003925554	Clinical Genetics Laboratory, Region Ostergotland	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004037387	Clingen Thrombosis Variant Curation Expert Panel, ClinGen	reviewed by expert panel (ClinGen ACMG Specifications SERPINC1 V1.0.0)	Pathogenic (Sep 21, 2023)	germline	curation	Citation Link,
SCV004099345	Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	no assertion criteria provided	Pathogenic (Oct 30, 2023)	germline	clinical testing
SCV005368365	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 2, 2024)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005914896	Department of Pathology and Laboratory Medicine, Sinai Health System	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 3, 2023)	germline	research	PubMed (1) [See all records that cite this PMID]
SCV007329868	Imagene.me medical diagnostic laboratory, IMAGENE.ME SA	criteria provided, single submitter (IMAGENE.ME Variant Classification SOP 2022)	Pathogenic	germline	clinical testing	Citation Link,
SCV007519267	Mendelics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 5, 2026)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007520039	Variantyx, Inc.	criteria provided, single submitter (Variantyx Assertion Criteria 2022)	Likely Pathogenic (Jun 19, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV007580777	First Genomix Gene Laboratory, Genetic Diagnostics Department	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 26, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV007595752	Clinical Genomic Analysis (GENYSIS) Core, University of North Carolina at Chapel Hill - UNC Genetic Determinants of Neurological and Developmental Disorders (GDNDD) Study	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Feb 16, 2026)	maternal	research	PubMed (2) [See all records that cite these PMIDs] 30005274, 25741868

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	2	not provided	not provided	2	not provided	clinical testing
not provided	germline	no	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, research, curation
not provided	maternal	unknown	1	not provided	not provided	1	not provided	research
not provided	unknown	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
European	unknown	yes	2	not provided	not provided	2	not provided	research

Citations

PubMed

An abnormal antithrombin III (AT III) with low heparin affinity: AT III Clichy.

Aiach M, François D, Priollet P, Capron L, Roncato M, Alhenc-Gelas M, Fiessinger JN.

Br J Haematol. 1987 Aug;66(4):515-22.

PubMed [citation]

PMID:: 3663508

CpG dinucleotides are "hotspots" for mutation in the antithrombin III gene. Twelve variants identified using the polymerase chain reaction.

Perry DJ, Carrell RW.

Mol Biol Med. 1989 Jun;6(3):239-43.

PubMed [citation]

PMID:: 2615648

See all PubMed Citations (19)

Details of each submission

From OMIM, SCV000039925.4

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

Description

This variant, formerly titled THROMBOPHILIA DUE TO ANTITHROMBIN III DEFICIENCY, has been reclassified because its contribution to the phenotype has not been confirmed.

AT-III Clichy, a substitution of leucine for proline-41, was described by Chang and Tran (1986), Aiach et al. (1987), and Molho-Sabatier et al. (1989). The variant has also been called AT-III Clichy-2, AT-III Basel, AT-III Franconville.

Aiach et al. (1987) found the mutation in heterozygous state in a 24-year-old woman presenting with a thoracic outlet syndrome.

Perry and Carrell (1989) described the same substitution in this heparin-binding mutation, which was caused by a CGT-to-CAT change in exon 2.

Olds et al. (1990) noted that this mutation occurs within a CG dinucleotide, a recognized hotspot for single base mutations.

In a woman referred for routine prepregnancy testing and in several members of her family, de Roux et al. (1990) found heterozygosity for the pro41-to-leu mutation. None had had thrombotic complications. Testing of the properties of the mutant AT-III suggested that proline-41 is more involved in the molecular changes induced by heparin than in the primary binding of the activator.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation, SCV000190626.1

#	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 Illumina Laboratory Services, Illumina, SCV000351487.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The SERPINC1 c.218C>T (p.Pro73Leu) missense variant is well described in the literature. Across a selection of the available literature, the p.Pro73Leu variant, which is also referred to as p.Pro41Leu, has been identified in a heterozygous state in four individuals diagnosed with antithrombin-III deficiency and with unspecified zygosity in 96 affected individuals (Chang et al. 1986; Molho-Sabatier et al. 1989; Puurunen et al. 2013; Feddersen et al. 2014). The p.Pro41Leu variant was absent from 106 controls, but is reported at a frequency of 0.00408 in the European (Finnish) population of the Exome Aggregation Consortium. Puurunen et al. (2013) suggest that the p.Pro73Leu variant is a founder variant in the Finnish population associated with type II hereditary antithrombin deficiency. The Pro73 residue is located at a heparin binding site. Bohdan et al. (2016) conducted a functional study to evaluate the effect of the p.Pro73Leu variant on binding affinity. The binding affinity between heparanase and antithrombin was greatly reduced in HEK-EBNA cells transfected with p.Pro73Leu variant plasmids compared to wildtype. Based on the collective evidence, the p.Pro73Leu variant is classified as pathogenic for antithrombin-III deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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, SCV000756581.9

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 73 of the SERPINC1 protein (p.Pro73Leu). This variant is present in population databases (rs121909551, gnomAD 0.4%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with type II antithrombin deficiency (PMID: 2794060, 3080419, 23910795, 24082793, 24956267, 26748602, 28317092). It is commonly reported in individuals of Finnish ancestry (PMID: 2794060, 3080419, 23910795, 24082793, 24956267, 26748602, 28317092). This variant is also known as Pro41Leu or AT Basel. ClinVar contains an entry for this variant (Variation ID: 18011). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt SERPINC1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SERPINC1 function (PMID: 2794060, 3080419, 24082793, 27322195). For these reasons, this variant has been classified as Pathogenic.

#	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 NIHR Bioresource Rare Diseases, University of Cambridge - ThromboGenomics, SCV000899323.2

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983481.1

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

Description

Variant summary: SERPINC1 c.218C>T (p.Pro73Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00082 in 251456 control chromosomes, predominatly in the Finnish and non-Finnish European subpopulations with a frequency of 0.0044 and 0.00089 respectively. The variant, c.218C>T (aka. Pro41Leu or AT Basel), is well known variant in the literature and has been reported in numerous individuals affected with Antithrombin III Deficiency (e.g. Chang_1986 , Molho-Sabatier_1989, Puurunen_2013, Bereczky_2021), and is considered to be a founder variant in the Finnish population (Puurunen_2013). Several of these publications reported significantly reduced antithrombin activity in carriers. Publications also reported experimental evidence evaluating an impact on protein function, and demonstrated reduced heparin binding properties (Martinez-Martinez_2012, Bohdan_2016). Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014, and all laboratories classified the variant as pathogenic (n=3) / likely pathogenic (n=2). Based on the evidence outlined above, the variant was classified as pathogenic.

#	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 Revvity Omics, Revvity, SCV002019179.4

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

#	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 ISTH-SSC Genomics in Thrombosis and Hemostasis, KU Leuven, Center for Molecular and Vascular Biology, SCV002515499.3

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided
2	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002810338.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics Laboratory, Region Ostergotland, SCV003925554.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clingen Thrombosis Variant Curation Expert Panel, ClinGen, SCV004037387.1

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

Description

The c.218C>T (p.Pro73Leu) variant is reported at a POPMAX FAF of 0.0007473 in exomes in gnomAD v2.1.1 and at an FAF of 0.0006639 in genomes in gnomAD v3.1.1 in the non-Finnish European population. The frequency does not meet the threshold for PM2_Supporting. At least 30 probands with AT deficiency and several others from internal laboratory data are reported with AT tests on 2 independent samples, meeting criteria for PS4_VeryStrong and PP4. There at least 17 meioses out of 35 families meeting PP1_Strong (PMID:28300866). This missense variant has a REVEL score of 0.658 (threshold >0.6), meeting criteria for PP3, and is within a heparin binding site, meeting PM1. In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the Thrombosis Variant Curation Expert Panel for SERPINC1: PS4_VeryStrong, PP1_Strong, PM1, PP3, PP4.

#	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 Zotz-Klimas Genetics Lab, MVZ Zotz Klimas, SCV004099345.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Institute of Human Genetics, University of Leipzig Medical Center, SCV005368365.2

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

Description

Criteria applied: PS4_VSTR,PP1_STR,PM1,PP3,PP4

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Department of Pathology and Laboratory Medicine, Sinai Health System, SCV005914896.1

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

#	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 Imagene.me medical diagnostic laboratory, IMAGENE.ME SA, SCV007329868.1

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

Description

Classified according to the IMAGENE.ME variant classification SOP based on the ACMG guidelines as Pathogenic (P): PS4_VeryStrong + PP1_Strong + PM1 + PP3 + PP4

#	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 Mendelics, SCV007519267.1

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

Description

Likely pathogenic/Pathogenic according to ACMG criteria. Variant from clinical tested patient.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Variantyx, Inc., SCV007520039.1

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

Description

This is a nonsynonymous variant in the SERPINC1 gene (OMIM: 107300). Pathogenic variants in this gene have been associated with autosomal dominant thrombophilia 7 due to antithrombin III deficiency. This is an established founder variant in the Finnish population (PMID: 23910795) (PS4). It lies within a known hotspot for pathogenic variants or a well-established critical functional domain of the SERPINC1 protein (PM1). Multiple computational algorithms predict a deleterious effect for this variant (REVEL score: 0.658) (PP3). This variant has a 0.1086% maximum allele frequency in non-founder control populations (https://gnomad.broadinstitute.org/). Based on the current evidence, this variant is classified as likely pathogenic for autosomal dominant thrombophilia 7 due to antithrombin III deficiency.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From First Genomix Gene Laboratory, Genetic Diagnostics Department, SCV007580777.1

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

Description

As part of Carrier Screening testing performed at First Genomix, this variant was identified in a heterozygous state in a patient who is not affected with this condition.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		1	not provided	not provided	not provided

From Clinical Genomic Analysis (GENYSIS) Core, University of North Carolina at Chapel Hill - UNC Genetic Determinants of Neurological and Developmental Disorders (GDNDD) Study, SCV007595752.1

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

Description

SERPINC1 c.218C>T, p.(Pro73Leu), is a missense variant predicted to alter a single amino acid in the encoded protein from a proline to a leucine and has been associated with moderate type II heparin binding site (HBS) AT deficiency (PMID:30005274). As this variant occurs at an HBS, has been reported in at least 35 probands with AT deficiency, with 17 segregations seen across 35 families, and is predicted by in silico models to have a damaging effect on the protein, the ClinGen Thrombosis Variant Curation Expert Panel have classified it as pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	maternal	unknown	1	not provided	not provided		1	not provided	not provided	not provided

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000039925	OMIM	flagged submission Reason: Conflicts with expert reviewed submission without evidence to support different classification Notes: None	Uncertain significance (Mar 1, 1992)	germline	literature only	PubMed (6) [See all records that cite these PMIDs] 3080419, 2794060, 3663508, 2615648, 1536946, 2372510
SCV000190626	CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation	flagged submission Reason: Conflicts with expert reviewed submission without evidence to support different classification Notes: None	Likely benign (Jun 1, 2014)	germline	research

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000039925

OMIM

flagged submission

Reason: Conflicts with expert reviewed submission without evidence to support different classification

Notes: None

Uncertain significance
(Mar 1, 1992)

germline

literature only

PubMed (6)
[See all records that cite these PMIDs]

SCV000190626

CSER _CC_NCGL, University of Washington - ESP 6500 variant annotation

flagged submission

Reason: Conflicts with expert reviewed submission without evidence to support different classification

Notes: None

Likely benign
(Jun 1, 2014)

germline

research

Last Updated: Jun 20, 2026

Relating variation to medicine