NM_022370.4(ROBO3):c.2312C>T (p.Pro771Leu) AND Gaze palsy, familial horizontal, with progressive scoliosis 1

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 9, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001290386.3

Allele description [Variation Report for NM_022370.4(ROBO3):c.2312C>T (p.Pro771Leu)]

NM_022370.4(ROBO3):c.2312C>T (p.Pro771Leu)

Gene:

ROBO3:roundabout guidance receptor 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q24.2

Genomic location:

Preferred name:

NM_022370.4(ROBO3):c.2312C>T (p.Pro771Leu)

HGVS:

NC_000011.10:g.124875576C>T
NG_016214.1:g.15168C>T
NM_022370.4:c.2312C>TMANE SELECT
NP_071765.2:p.Pro771Leu
NC_000011.9:g.124745472C>T
NM_022370.3:c.2312C>T
p.Pro771Leu

Protein change:

P771L

Links:

dbSNP: rs1946347156

NCBI 1000 Genomes Browser:

rs1946347156

Molecular consequence:

NM_022370.4:c.2312C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Gaze palsy, familial horizontal, with progressive scoliosis 1 (HGPPS1)
Identifiers:: MONDO: MONDO:0020790; MedGen: C4551964; Orphanet: 2744; OMIM: 607313

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001468612	Institute of Human Genetics, University of Leipzig Medical Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 9, 2021)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 19041479, 25741868
SCV002073839	Pathology and Clinical Laboratory Medicine, King Fahad Medical City	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic	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

SCV001468612

Institute of Human Genetics, University of Leipzig Medical Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 9, 2021)

germline

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV002073839

Pathology and Clinical Laboratory Medicine, King Fahad Medical City

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic

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	yes	not provided	not provided	not provided	not provided	not provided	curation
Arab	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Bilateral synergistic convergence associated with homozygous ROB03 mutation (p.Pro771Leu).

Khan AO, Oystreck DT, Al-Tassan N, Al-Sharif L, Bosley TM.

Ophthalmology. 2008 Dec;115(12):2262-5. doi: 10.1016/j.ophtha.2008.08.010.

PubMed [citation]

PMID:: 19041479

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Institute of Human Genetics, University of Leipzig Medical Center, SCV001468612.1

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

Description

This ROBO3 variant was reported as Pathogenicâ€‹ in PMID: 19041479 with original nomenclature reported as c.2312C>T (p.Pro771Leu). Variant was re-classified as Likely Pathogenic based on the criteria PM2_Supporting, PM3_Moderate, PP4_Supporting, BP4_Supporting.

#	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 Pathology and Clinical Laboratory Medicine, King Fahad Medical City, SCV002073839.1

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

Last Updated: Jun 23, 2024

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