NM_001379270.1(CNGA1):c.1525G>A (p.Gly509Arg) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 5, 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:: RCV001380418.7

Allele description [Variation Report for NM_001379270.1(CNGA1):c.1525G>A (p.Gly509Arg)]

NM_001379270.1(CNGA1):c.1525G>A (p.Gly509Arg)

Genes:

CNGA1:cyclic nucleotide gated channel subunit alpha 1 [Gene - OMIM - HGNC]
LOC101927157:uncharacterized LOC101927157 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

4p12

Genomic location:

Preferred name:

NM_001379270.1(CNGA1):c.1525G>A (p.Gly509Arg)

Other names:

CNGA1, GLY509ARG (rs544588016)

HGVS:

NC_000004.12:g.47936957C>T
NG_009193.1:g.80988G>A
NM_000087.5:c.1525G>A
NM_001142564.2:c.1525G>A
NM_001379270.1:c.1525G>AMANE SELECT
NP_000078.3:p.Gly509Arg
NP_001136036.2:p.Gly509Arg
NP_001366199.1:p.Gly509Arg
NC_000004.11:g.47938974C>T

Protein change:

G509R; GLY509ARG

Links:

OMIM: 123825.0011; dbSNP: rs544588016

NCBI 1000 Genomes Browser:

rs544588016

Molecular consequence:

NM_000087.5:c.1525G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001142564.2:c.1525G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001379270.1:c.1525G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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TGFB2 [Prionailurus viverrinus]
TGFB2 [Prionailurus viverrinus]
Gene ID:125155525

Gene
DC156181 Xenopus tropicalis embryo gastrula Xenopus tropicalis cDNA clone rst79b...
DC156181 Xenopus tropicalis embryo gastrula Xenopus tropicalis cDNA clone rst79b18 3', mRNA sequence
gi|119138782|gnl|dbEST|43403736|dbj 6181.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001578483	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 5, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26802146, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001578483

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 5, 2022)

germline

clinical testing

PubMed (2)
[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

Novel compound heterozygous mutation in the CNGA1 gene underlie autosomal recessive retinitis pigmentosa in a Chinese family.

Jin X, Qu LH, Hou BK, Xu HW, Meng XH, Pang CP, Yin ZQ.

Biosci Rep. 2016 Jan 22;36(1):e00289. doi: 10.1042/BSR20150131. Print 2016.

PubMed [citation]

PMID:: 26802146
PMCID:: PMC4725244

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001578483.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects CNGA1 function (PMID: 26802146). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1068762). This missense change has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 26802146; externalcommunication). 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. This variant is present in population databases (rs544588016, gnomAD 0.003%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 513 of the CNGA1 protein (p.Gly513Arg).

#	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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