NM_000440.3(PDE6A):c.1689C>A (p.His563Gln) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 23, 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:: RCV001226626.6

Allele description [Variation Report for NM_000440.3(PDE6A):c.1689C>A (p.His563Gln)]

NM_000440.3(PDE6A):c.1689C>A (p.His563Gln)

Gene:

PDE6A:phosphodiesterase 6A [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_000440.3(PDE6A):c.1689C>A (p.His563Gln)

HGVS:

NC_000005.10:g.149895222G>T
NG_009102.1:g.54572C>A
NM_000440.3:c.1689C>AMANE SELECT
NP_000431.2:p.His563Gln
NC_000005.9:g.149274785G>T
NM_000440.2:c.1689C>A

Protein change:

H563Q

Links:

dbSNP: rs776918069

NCBI 1000 Genomes Browser:

rs776918069

Molecular consequence:

NM_000440.3:c.1689C>A - 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
SCV001398947	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 23, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 30543658, 33057649, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001398947

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 23, 2022)

germline

clinical testing

PubMed (3)
[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

Next-generation sequencing identifies unexpected genotype-phenotype correlations in patients with retinitis pigmentosa.

Birtel J, Gliem M, Mangold E, Müller PL, Holz FG, Neuhaus C, Lenzner S, Zahnleiter D, Betz C, Eisenberger T, Bolz HJ, Charbel Issa P.

PLoS One. 2018;13(12):e0207958. doi: 10.1371/journal.pone.0207958.

PubMed [citation]

PMID:: 30543658
PMCID:: PMC6292620

Clinical Phenotype and Course of PDE6A-Associated Retinitis Pigmentosa Disease, Characterized in Preparation for a Gene Supplementation Trial.

Kuehlewein L, Zobor D, Andreasson SO, Ayuso C, Banfi S, Bocquet B, Bernd AS, Biskup S, Boon CJF, Downes SM, Fischer MD, Holz FG, Kellner U, Leroy BP, Meunier I, Nasser F, Rosenberg T, Rudolph G, Stingl K, Thiadens AAHJ, Wilhelm B, Wissinger B, et al.

JAMA Ophthalmol. 2020 Dec 1;138(12):1241-1250. doi: 10.1001/jamaophthalmol.2020.4206.

PubMed [citation]

PMID:: 33057649
PMCID:: PMC7563671

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001398947.5

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

Description

This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 563 of the PDE6A protein (p.His563Gln). This variant is present in population databases (rs776918069, gnomAD 0.002%). This missense change has been observed in individual(s) with retinitis pigmentosa (PMID: 30543658, 33057649). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 866352). 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 C15"). 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.

#	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 16, 2024

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