NM_000350.3(ABCA4):c.3364G>A (p.Glu1122Lys) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 10, 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:: RCV000085574.11

Allele description [Variation Report for NM_000350.3(ABCA4):c.3364G>A (p.Glu1122Lys)]

NM_000350.3(ABCA4):c.3364G>A (p.Glu1122Lys)

Gene:

ABCA4:ATP binding cassette subfamily A member 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p22.1

Genomic location:

Preferred name:

NM_000350.3(ABCA4):c.3364G>A (p.Glu1122Lys)

HGVS:

NC_000001.11:g.94041367C>T
NG_009073.1:g.84783G>A
NG_009073.2:g.84781G>A
NM_000350.3:c.3364G>AMANE SELECT
NM_001425324.1:c.3142G>A
NP_000341.2:p.Glu1122Lys
NP_001412253.1:p.Glu1048Lys
NC_000001.10:g.94506923C>T
NM_000350.2:c.3364G>A
P78363:p.Glu1122Lys

Protein change:

E1048K; GLU1122LYS

Links:

UniProtKB: P78363#VAR_008438; OMIM: 601691.0037; dbSNP: rs61751399

NCBI 1000 Genomes Browser:

rs61751399

Molecular consequence:

NM_000350.3:c.3364G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.3142G>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
SCV000117712	Retina International	no classification provided	not provided	not provided	not provided
SCV001217904	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 10, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 9973280, 28041643, 28512305, 28492532
SCV001446634	Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 23, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000117712

Retina International

no classification provided

not provided

SCV001217904

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 10, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001446634

Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 23, 2020)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_ABCR:c.3364G>A: SCV000117712

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	1	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Genotype/Phenotype analysis of a photoreceptor-specific ATP-binding cassette transporter gene, ABCR, in Stargardt disease.

Lewis RA, Shroyer NF, Singh N, Allikmets R, Hutchinson A, Li Y, Lupski JR, Leppert M, Dean M.

Am J Hum Genet. 1999 Feb;64(2):422-34.

PubMed [citation]

PMID:: 9973280
PMCID:: PMC1377752

Comprehensive Rare Variant Analysis via Whole-Genome Sequencing to Determine the Molecular Pathology of Inherited Retinal Disease.

Carss KJ, Arno G, Erwood M, Stephens J, Sanchis-Juan A, Hull S, Megy K, Grozeva D, Dewhurst E, Malka S, Plagnol V, Penkett C, Stirrups K, Rizzo R, Wright G, Josifova D, Bitner-Glindzicz M, Scott RH, Clement E, Allen L, Armstrong R, Brady AF, et al.

Am J Hum Genet. 2017 Jan 5;100(1):75-90. doi: 10.1016/j.ajhg.2016.12.003. Epub 2016 Dec 29.

PubMed [citation]

PMID:: 28041643
PMCID:: PMC5223092

See all PubMed Citations (5)

Details of each submission

From Retina International, SCV000117712.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001217904.5

#	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 glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1122 of the ABCA4 protein (p.Glu1122Lys). This variant is present in population databases (rs61751399, gnomAD 0.006%). This missense change has been observed in individual(s) with inherited retinal disease (PMID: 9973280, 28041643, 28512305). 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: 30218). 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 ABCA4 protein function with a positive predictive value of 95%. 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 Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen, SCV001446634.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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