NM_022356.4(P3H1):c.2054G>T (p.Arg685Leu) AND Osteogenesis imperfecta type 8

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

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 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:: RCV003043049.1

Allele description

NM_022356.4(P3H1):c.2054G>T (p.Arg685Leu)

Gene:

P3H1:prolyl 3-hydroxylase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_022356.4(P3H1):c.2054G>T (p.Arg685Leu)

HGVS:

NC_000001.11:g.42747273C>A
NG_008123.1:g.24812G>T
NM_001146289.2:c.2054G>T
NM_001243246.2:c.2054G>T
NM_022356.4:c.2054G>TMANE SELECT
NP_001139761.1:p.Arg685Leu
NP_001139761.1:p.Arg685Leu
NP_001230175.1:p.Arg685Leu
NP_001230175.1:p.Arg685Leu
NP_071751.2:p.Arg685Leu
NP_071751.3:p.Arg685Leu
NP_071751.3:p.Arg685Leu
LRG_5t1:c.2054G>T
LRG_5t2:c.2054G>T
LRG_5t3:c.2054G>T
LRG_5:g.24812G>T
LRG_5p1:p.Arg685Leu
LRG_5p2:p.Arg685Leu
LRG_5p3:p.Arg685Leu
NC_000001.10:g.43212944C>A
NM_001146289.1:c.2054G>T
NM_001243246.1:c.2054G>T
NM_022356.2:c.2054G>T
NM_022356.3:c.2054G>T

Protein change:

R685L

Molecular consequence:

NM_001146289.2:c.2054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001243246.2:c.2054G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_022356.4:c.2054G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Osteogenesis imperfecta type 8 (OI8)
Synonyms:: OI type VIII
Identifiers:: MONDO: MONDO:0012581; MedGen: C1970458; OMIM: 610915

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003337054	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 29, 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

SCV003337054

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 29, 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, SCV003337054.1

#	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 leucine, which is neutral and non-polar, at codon 685 of the P3H1 protein (p.Arg685Leu). This variant is present in population databases (rs376514633, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with P3H1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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 1, 2024

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