NM_000313.4(PROS1):c.964_965delinsCC (p.Arg322Pro) AND Thrombophilia due to protein S deficiency, autosomal recessive

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 12, 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:: RCV003644117.2

Allele description [Variation Report for NM_000313.4(PROS1):c.964_965delinsCC (p.Arg322Pro)]

NM_000313.4(PROS1):c.964_965delinsCC (p.Arg322Pro)

Gene:

PROS1:protein S [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

3q11.1

Genomic location:

Preferred name:

NM_000313.4(PROS1):c.964_965delinsCC (p.Arg322Pro)

HGVS:

NC_000003.12:g.93896576_93896577delinsGG
NG_009813.1:g.82514_82515delinsCC
NM_000313.4:c.964_965delinsCCMANE SELECT
NM_001314077.2:c.1060_1061delinsCC
NP_000304.2:p.Arg322Pro
NP_000304.2:p.Arg322Pro
NP_001301006.1:p.Arg354Pro
NP_001301006.1:p.Arg354Pro
LRG_572t1:c.964_965delAGinsCC
LRG_572t2:c.1060_1061delAGinsCC
LRG_572:g.82514_82515delinsCC
LRG_572p1:p.Arg322Pro
LRG_572p2:p.Arg354Pro
NC_000003.11:g.93615420_93615421delinsGG
NM_000313.3:c.964_965delAGinsCC
NM_001314077.1:c.1060_1061delAGinsCC

Protein change:

R322P

Molecular consequence:

NM_000313.4:c.964_965delinsCC - missense variant - [Sequence Ontology: SO:0001583]
NM_001314077.2:c.1060_1061delinsCC - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Thrombophilia due to protein S deficiency, autosomal recessive (THPH6)
Identifiers:: MONDO: MONDO:0013791; MedGen: C3281092; Orphanet: 743; OMIM: 614514

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004503863	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 12, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004503863

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 12, 2023)

germline

clinical testing

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

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

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, SCV004503863.1

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

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 322 of the PROS1 protein (p.Arg322Pro). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with protein S deficiency disease (Invitae). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.

#	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: Sep 29, 2024

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