NM_000283.4(PDE6B):c.1654C>T (p.Arg552Trp) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 9, 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:: RCV001966130.6

Allele description [Variation Report for NM_000283.4(PDE6B):c.1654C>T (p.Arg552Trp)]

NM_000283.4(PDE6B):c.1654C>T (p.Arg552Trp)

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.1654C>T (p.Arg552Trp)

HGVS:

NC_000004.12:g.662173C>T
NG_009839.1:g.41600C>T
NM_000283.4:c.1654C>TMANE SELECT
NM_001145291.2:c.1654C>T
NM_001145292.2:c.817C>T
NM_001350154.3:c.817C>T
NM_001350155.3:c.499C>T
NM_001379246.1:c.817C>T
NM_001379247.1:c.817C>T
NP_000274.3:p.Arg552Trp
NP_001138763.2:p.Arg552Trp
NP_001138764.2:p.Arg273Trp
NP_001337083.1:p.Arg273Trp
NP_001337084.1:p.Arg167Trp
NP_001366175.1:p.Arg273Trp
NP_001366176.1:p.Arg273Trp
NC_000004.11:g.655962C>T

Protein change:

R167W

Links:

dbSNP: rs1201231261

NCBI 1000 Genomes Browser:

rs1201231261

Molecular consequence:

NM_000283.4:c.1654C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1654C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.817C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.817C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.499C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.817C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.817C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002254330	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 9, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 8956055, 21655355, 28559085, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002254330

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 9, 2022)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Identification of a novel R552O mutation in exon 13 of the beta-subunit of rod phosphodiesterase gene in a Spanish family with autosomal recessive retinitis pigmentosa.

Valverde D, Baiget M, Seminago R, del Rio E, García-Sandoval B, del Rio T, Bayés M, Balcells S, Martínez A, Grinberg D, Ayuso C.

Hum Mutat. 1996;8(4):393-4. No abstract available.

PubMed [citation]

PMID:: 8956055

Mutations in the β-subunit of rod phosphodiesterase identified in consanguineous Pakistani families with autosomal recessive retinitis pigmentosa.

Ali S, Riazuddin SA, Shahzadi A, Nasir IA, Khan SN, Husnain T, Akram J, Sieving PA, Hejtmancik JF, Riazuddin S.

Mol Vis. 2011;17:1373-80. Epub 2011 May 25.

PubMed [citation]

PMID:: 21655355
PMCID:: PMC3108895

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002254330.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 552 of the PDE6B protein (p.Arg552Trp). This missense change has been observed in individual(s) with clinical features of autosomal recessive retinitis pigmentosa (Invitae). 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. This variant disrupts the p.Arg552 amino acid residue in PDE6B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8956055, 21655355, 28559085). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 1466663).

#	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: Oct 13, 2024

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