NM_000283.4(PDE6B):c.1580T>C (p.Leu527Pro) AND Retinitis pigmentosa

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Apr 1, 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:: RCV000504854.8

Allele description [Variation Report for NM_000283.4(PDE6B):c.1580T>C (p.Leu527Pro)]

NM_000283.4(PDE6B):c.1580T>C (p.Leu527Pro)

Gene:

PDE6B:phosphodiesterase 6B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

4p16.3

Genomic location:

Preferred name:

NM_000283.4(PDE6B):c.1580T>C (p.Leu527Pro)

HGVS:

NC_000004.12:g.660579T>C
NG_009839.1:g.40006T>C
NM_000283.4:c.1580T>CMANE SELECT
NM_001145291.2:c.1580T>C
NM_001145292.2:c.743T>C
NM_001350154.3:c.743T>C
NM_001350155.3:c.425T>C
NM_001379246.1:c.743T>C
NM_001379247.1:c.743T>C
NP_000274.2:p.Leu527Pro
NP_000274.3:p.Leu527Pro
NP_001138763.2:p.Leu527Pro
NP_001138764.2:p.Leu248Pro
NP_001337083.1:p.Leu248Pro
NP_001337084.1:p.Leu142Pro
NP_001366175.1:p.Leu248Pro
NP_001366176.1:p.Leu248Pro
NC_000004.11:g.654368T>C
NM_000283.3:c.1580T>C

Protein change:

L142P

Links:

dbSNP: rs760766981

NCBI 1000 Genomes Browser:

rs760766981

Molecular consequence:

NM_000283.4:c.1580T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1580T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.425T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.743T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.743T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Retinitis pigmentosa (RP)
Synonyms:: Tapetoretinal degeneration
Identifiers:: MONDO: MONDO:0019200; MeSH: D012174; MedGen: C0035334; Orphanet: 791; OMIM: 268000; OMIM: PS268000

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000599139	NIHR Bioresource Rare Diseases, University of Cambridge	no assertion criteria provided	Likely pathogenic (Jan 1, 2015)	unknown	research	PubMed (2) [See all records that cite these PMIDs] 7724547, 28041643
SCV000916071	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Uncertain significance (Nov 14, 2018)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV001950323	Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 1, 2021)	germline	curation	PubMed (5) [See all records that cite these PMIDs] 28041643, 7724547, 28559085, 25741868, 34906470

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000599139

NIHR Bioresource Rare Diseases, University of Cambridge

no assertion criteria provided

Likely pathogenic
(Jan 1, 2015)

unknown

research

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

SCV000916071

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Uncertain significance
(Nov 14, 2018)

germline

clinical testing

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

Citation Link,

SCV001950323

Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 1, 2021)

germline

curation

PubMed (5)
[See all records that cite these PMIDs]

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
not provided	germline	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

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

Mutation spectrum of the gene encoding the beta subunit of rod phosphodiesterase among patients with autosomal recessive retinitis pigmentosa.

McLaughlin ME, Ehrhart TL, Berson EL, Dryja TP.

Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3249-53.

PubMed [citation]

PMID:: 7724547
PMCID:: PMC42143

See all PubMed Citations (5)

Details of each submission

From NIHR Bioresource Rare Diseases, University of Cambridge, SCV000599139.1

#	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 Illumina Laboratory Services, Illumina, SCV000916071.1

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

Description

The PDE6B c.1580T>C (p.Leu527Pro) missense variant has been reported in a compound heterozygous state in three individuals, including a sibling pair, with retinitis pigmentosa (McLaughlin et al. 1995; Carss et al. 2017). Control data are unavailable for this variant, which is reported at a frequency of 0.00015 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the limited evidence, the p.Leu527Pro variant is classified as a variant of unknown significance but suspicious for pathogenicity for the recessive form of retinitis pigmentosa. 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 Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV001950323.1

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

Description

The p.Leu527Pro variant in PDE6B was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PM3. Based on this evidence we have classified this variant as a Variant of Uncertain Significance. If you have any questions about the classification please reach out to the Pierce Lab.

#	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

Last Updated: Nov 24, 2024

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