NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr) AND not provided

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 20, 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:: RCV001851841.3

Allele description

NM_000283.4(PDE6B):c.1669C>T (p.His557Tyr)

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.1669C>T (p.His557Tyr)

HGVS:

NC_000004.12:g.662188C>T
NG_009839.1:g.41615C>T
NM_000283.4:c.1669C>TMANE SELECT
NM_001145291.2:c.1669C>T
NM_001145292.2:c.832C>T
NM_001350154.3:c.832C>T
NM_001350155.3:c.514C>T
NM_001379246.1:c.832C>T
NM_001379247.1:c.832C>T
NP_000274.2:p.His557Tyr
NP_000274.3:p.His557Tyr
NP_001138763.2:p.His557Tyr
NP_001138764.2:p.His278Tyr
NP_001337083.1:p.His278Tyr
NP_001337084.1:p.His172Tyr
NP_001366175.1:p.His278Tyr
NP_001366176.1:p.His278Tyr
NC_000004.11:g.655977C>T
NM_000283.3:c.1669C>T
P35913:p.His557Tyr

Protein change:

H172Y; HIS557TYR

Links:

UniProtKB: P35913#VAR_006050; OMIM: 180072.0004; dbSNP: rs121918581

NCBI 1000 Genomes Browser:

rs121918581

Molecular consequence:

NM_000283.4:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1669C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.514C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.832C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.832C>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
SCV002247484	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 20, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 25356976, 25827439, 29785639, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002247484

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 20, 2023)

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

Genotype-phenotype correlation and mutation spectrum in a large cohort of patients with inherited retinal dystrophy revealed by next-generation sequencing.

Huang XF, Huang F, Wu KC, Wu J, Chen J, Pang CP, Lu F, Qu J, Jin ZB.

Genet Med. 2015 Apr;17(4):271-8. doi: 10.1038/gim.2014.138. Epub 2014 Nov 6.

PubMed [citation]

PMID:: 25356976

Reduced rod electroretinograms in carrier parents of two Japanese siblings with autosomal recessive retinitis pigmentosa associated with PDE6B gene mutations.

Kuniyoshi K, Sakuramoto H, Yoshitake K, Ikeo K, Furuno M, Tsunoda K, Kusaka S, Shimomura Y, Iwata T.

Doc Ophthalmol. 2015 Aug;131(1):71-9. doi: 10.1007/s10633-015-9497-7. Epub 2015 Apr 1.

PubMed [citation]

PMID:: 25827439

See all PubMed Citations (4)

Details of each submission

From Invitae, SCV002247484.3

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

Description

This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 557 of the PDE6B protein (p.His557Tyr). This variant is present in population databases (rs121918581, gnomAD 0.04%). This missense change has been observed in individual(s) with inherited retinal dystrophy and/or retinitis pigmentosa (PMID: 25356976, 25827439, 29785639). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 13106). 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. 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: Jun 23, 2024

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