NM_000350.3(ABCA4):c.1868A>G (p.Gln623Arg) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 3, 2023
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:: RCV003562267.2

Allele description [Variation Report for NM_000350.3(ABCA4):c.1868A>G (p.Gln623Arg)]

NM_000350.3(ABCA4):c.1868A>G (p.Gln623Arg)

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.1868A>G (p.Gln623Arg)

HGVS:

NC_000001.11:g.94062646T>C
NG_009073.2:g.63502A>G
NM_000350.3:c.1868A>GMANE SELECT
NM_001425324.1:c.1868A>G
NP_000341.2:p.Gln623Arg
NP_001412253.1:p.Gln623Arg
NC_000001.10:g.94528202T>C
NG_009073.1:g.63504A>G

Protein change:

Q623R

Molecular consequence:

NM_000350.3:c.1868A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.1868A>G - 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
SCV004292533	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Feb 3, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 21911583, 32619608, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292533

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Feb 3, 2023)

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

Analysis of the ABCA4 gene by next-generation sequencing.

Zernant J, Schubert C, Im KM, Burke T, Brown CM, Fishman GA, Tsang SH, Gouras P, Dean M, Allikmets R.

Invest Ophthalmol Vis Sci. 2011 Oct 31;52(11):8479-87. doi: 10.1167/iovs.11-8182.

PubMed [citation]

PMID:: 21911583
PMCID:: PMC3208189

Genotype-Phenotype Correlations in a Spanish Cohort of 506 Families With Biallelic ABCA4 Pathogenic Variants.

Del Pozo-Valero M, Riveiro-Alvarez R, Blanco-Kelly F, Aguirre-Lamban J, Martin-Merida I, Iancu IF, Swafiri S, Lorda-Sanchez I, Rodriguez-Pinilla E, Trujillo-Tiebas MJ, Jimenez-Rolando B, Carreño E, Mahillo-Fernandez I, Rivolta C, Corton M, Avila-Fernandez A, Garcia-Sandoval B, Ayuso C.

Am J Ophthalmol. 2020 Nov;219:195-204. doi: 10.1016/j.ajo.2020.06.027. Epub 2020 Jun 30.

PubMed [citation]

PMID:: 32619608

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292533.1

#	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 glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 623 of the ABCA4 protein (p.Gln623Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of ABCA4-related conditions (PMID: 21911583, 32619608). 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. 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.

#	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: Nov 3, 2024

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