NM_000283.4(PDE6B):c.1712C>T (p.Thr571Met) AND not provided

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Jan 6, 2022
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:: RCV001206651.11

Allele description [Variation Report for NM_000283.4(PDE6B):c.1712C>T (p.Thr571Met)]

NM_000283.4(PDE6B):c.1712C>T (p.Thr571Met)

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.1712C>T (p.Thr571Met)

HGVS:

NC_000004.12:g.662231C>T
NG_009839.1:g.41658C>T
NM_000283.4:c.1712C>TMANE SELECT
NM_001145291.2:c.1712C>T
NM_001145292.2:c.875C>T
NM_001350154.3:c.875C>T
NM_001350155.3:c.557C>T
NM_001379246.1:c.875C>T
NM_001379247.1:c.875C>T
NP_000274.2:p.Thr571Met
NP_000274.3:p.Thr571Met
NP_001138763.2:p.Thr571Met
NP_001138764.2:p.Thr292Met
NP_001337083.1:p.Thr292Met
NP_001337084.1:p.Thr186Met
NP_001366175.1:p.Thr292Met
NP_001366176.1:p.Thr292Met
NC_000004.11:g.656020C>T
NM_000283.3:c.1712C>T

Protein change:

T186M

Links:

dbSNP: rs761619791

NCBI 1000 Genomes Browser:

rs761619791

Molecular consequence:

NM_000283.4:c.1712C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145291.2:c.1712C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001145292.2:c.875C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350154.3:c.875C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350155.3:c.557C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379246.1:c.875C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001379247.1:c.875C>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
SCV001377970	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 6, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25356976, 29641573, 28492532
SCV001820517	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (May 18, 2021)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001377970

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 6, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV001820517

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(May 18, 2021)

germline

clinical testing

Citation Link

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	clinical testing
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

Systematic evaluation of a targeted gene capture sequencing panel for molecular diagnosis of retinitis pigmentosa.

Huang H, Chen Y, Chen H, Ma Y, Chiang PW, Zhong J, Liu X, Asan, Wu J, Su Y, Li X, Deng J, Huang Y, Zhang X, Li Y, Fan N, Wang Y, Tang L, Shen J, Chen M, Zhang X, Te D, et al.

PLoS One. 2018;13(4):e0185237. doi: 10.1371/journal.pone.0185237.

PubMed [citation]

PMID:: 29641573
PMCID:: PMC5894961

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001377970.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 866660). This missense change has been observed in individuals with clinical features of autosomal recessive retinitis pigmentosa (PMID: 25356976, 29641573; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 571 of the PDE6B protein (p.Thr571Met).

#	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 GeneDx, SCV001820517.1

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25356976, 33177553, 31054281, 29641573)

#	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: Sep 29, 2024

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