NM_001379270.1(CNGA1):c.1258C>T (p.Arg420Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 17, 2023
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:: RCV001228205.7

Allele description [Variation Report for NM_001379270.1(CNGA1):c.1258C>T (p.Arg420Ter)]

NM_001379270.1(CNGA1):c.1258C>T (p.Arg420Ter)

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.1258C>T (p.Arg420Ter)

HGVS:

NC_000004.12:g.47937224G>A
NG_009193.1:g.80721C>T
NM_000087.4:c.1270C>T
NM_000087.5:c.1258C>T
NM_001142564.2:c.1258C>T
NM_001379270.1:c.1258C>TMANE SELECT
NP_000078.3:p.Arg420Ter
NP_001136036.2:p.Arg420Ter
NP_001366199.1:p.Arg420Ter
NC_000004.11:g.47939241G>A
NM_000087.3:c.1270C>T

Protein change:

R420*

Links:

dbSNP: rs369717052

NCBI 1000 Genomes Browser:

rs369717052

Molecular consequence:

NM_000087.5:c.1258C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001142564.2:c.1258C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001379270.1:c.1258C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001400591	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 17, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 26496393, 28492532
SCV003921561	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Oct 28, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001400591

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 17, 2023)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV003921561

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Oct 28, 2022)

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

Dependable and Efficient Clinical Molecular Diagnosis of Chinese RP Patient with Targeted Exon Sequencing.

Yang L, Cui H, Yin X, Dou H, Zhao L, Chen N, Zhang J, Zhang H, Li G, Ma Z.

PLoS One. 2015;10(10):e0140684. doi: 10.1371/journal.pone.0140684.

PubMed [citation]

PMID:: 26496393
PMCID:: PMC4619688

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, SCV001400591.5

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

Description

This sequence change creates a premature translational stop signal (p.Arg424*) in the CNGA1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 267 amino acid(s) of the CNGA1 protein. This variant is present in population databases (rs369717052, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with autosomal recessive retinitis pigmentosa (PMID: 26496393). It has also been observed to segregate with disease in related individuals. This variant is also known as c.1477C>T (p.Arg493*). ClinVar contains an entry for this variant (Variation ID: 866760). 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

From GeneDx, SCV003921561.1

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

Description

Nonsense variant predicted to result in protein truncation, as the last 267 amino acids are lost, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26496393)

#	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: Nov 10, 2024

ClinVar

Relating variation to medicine