NM_000313.4(PROS1):c.1811T>G (p.Leu604Arg) AND Thrombophilia due to protein S deficiency, autosomal recessive

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 27, 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:: RCV003772020.1

Allele description

NM_000313.4(PROS1):c.1811T>G (p.Leu604Arg)

Gene:

PROS1:protein S [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3q11.1

Genomic location:

Preferred name:

NM_000313.4(PROS1):c.1811T>G (p.Leu604Arg)

HGVS:

NC_000003.12:g.93877025A>C
NG_009813.1:g.102066T>G
NM_000313.4:c.1811T>GMANE SELECT
NM_001314077.2:c.1907T>G
NP_000304.2:p.Leu604Arg
NP_001301006.1:p.Leu636Arg
LRG_572t1:c.1811T>G
LRG_572:g.102066T>G
NC_000003.11:g.93595869A>C
NM_000313.3:c.1811T>G

Protein change:

L604R

Links:

dbSNP: rs2107125076

NCBI 1000 Genomes Browser:

rs2107125076

Molecular consequence:

NM_000313.4:c.1811T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001314077.2:c.1907T>G - 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

Recent activity

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Rattus norvegicus Niemann-Pick disease, type C2 (Npc2), mRNA
Rattus norvegicus Niemann-Pick disease, type C2 (Npc2), mRNA
gi|27465564|ref|NM_173118.1|

Nucleotide
phosphoenolpyruvate carboxykinase, partial [Gammarus insensibilis]
phosphoenolpyruvate carboxykinase, partial [Gammarus insensibilis]
gi|2211530942|gb|UNQ89457.1|

Protein
cytochrome oxidase subunit 1, partial (mitochondrion) [Gammarus crinicornis]
cytochrome oxidase subunit 1, partial (mitochondrion) [Gammarus crinicornis]
gi|294987978|gb|ADF56379.1|

Protein
LOW QUALITY PROTEIN: BTB/POZ domain-containing adapter for CUL3-mediated RhoA de...
LOW QUALITY PROTEIN: BTB/POZ domain-containing adapter for CUL3-mediated RhoA degradation protein 3 [Xenopus laevis]
gi|2038130788|ref|XP_041421956.1|

Protein
Mus musculus coiled-coil glutamate-rich protein 1 (Ccer1), mRNA
Mus musculus coiled-coil glutamate-rich protein 1 (Ccer1), mRNA
gi|70980540|ref|NM_025724.2|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004681705	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 27, 2022)	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

SCV004681705

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 27, 2022)

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 Invitae, SCV004681705.1

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

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. 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. ClinVar contains an entry for this variant (Variation ID: 1312442). This variant has not been reported in the literature in individuals affected with PROS1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 604 of the PROS1 protein (p.Leu604Arg).

#	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: Mar 5, 2024

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