NM_000283.4(PDE6B):c.1678C>T (p.Arg560Cys) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 13, 2023
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:: RCV001853246.6

Allele description [Variation Report for NM_000283.4(PDE6B):c.1678C>T (p.Arg560Cys)]

NM_000283.4(PDE6B):c.1678C>T (p.Arg560Cys)

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.1678C>T (p.Arg560Cys)

HGVS:

NC_000004.12:g.662197C>T
NG_009839.1:g.41624C>T
NM_000283.4:c.1678C>TMANE SELECT
NM_001145291.2:c.1678C>T
NM_001145292.2:c.841C>T
NM_001350154.3:c.841C>T
NM_001350155.3:c.523C>T
NM_001379246.1:c.841C>T
NM_001379247.1:c.841C>T
NP_000274.2:p.Arg560Cys
NP_000274.3:p.Arg560Cys
NP_001138763.2:p.Arg560Cys
NP_001138764.2:p.Arg281Cys
NP_001337083.1:p.Arg281Cys
NP_001337084.1:p.Arg175Cys
NP_001366175.1:p.Arg281Cys
NP_001366176.1:p.Arg281Cys
NC_000004.11:g.655986C>T
NM_000283.3:c.1678C>T

Protein change:

R175C; ARG560CYS

Links:

OMIM: 180072.0008; dbSNP: rs201541131

NCBI 1000 Genomes Browser:

rs201541131

Molecular consequence:

NM_000283.4:c.1678C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1678C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.523C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.841C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.841C>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
SCV002236727	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 25823529, 28041643, 30998820, 17267005, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002236727

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 13, 2023)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Re-evaluation casts doubt on the pathogenicity of homozygous USH2A p.C759F.

Pozo MG, Bravo-Gil N, Méndez-Vidal C, Montero-de-Espinosa I, Millán JM, Dopazo J, Borrego S, Antiñolo G.

Am J Med Genet A. 2015 Jul;167(7):1597-600. doi: 10.1002/ajmg.a.37003. Epub 2015 Mar 30.

PubMed [citation]

PMID:: 25823529

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

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002236727.3

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

Description

This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 560 of the PDE6B protein (p.Arg560Cys). 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 missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 25823529, 28041643, 30998820). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217798). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PDE6B protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PDE6B function (PMID: 17267005). For these reasons, this variant has been classified as Pathogenic.

#	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 29, 2024

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