NM_000350.3(ABCA4):c.6326T>C (p.Leu2109Pro) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 21, 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:: RCV001055307.6

Allele description [Variation Report for NM_000350.3(ABCA4):c.6326T>C (p.Leu2109Pro)]

NM_000350.3(ABCA4):c.6326T>C (p.Leu2109Pro)

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.6326T>C (p.Leu2109Pro)

HGVS:

NC_000001.11:g.94001062A>G
NG_009073.1:g.125088T>C
NG_009073.2:g.125086T>C
NM_000350.3:c.6326T>CMANE SELECT
NM_001425324.1:c.6104T>C
NP_000341.2:p.Leu2109Pro
NP_001412253.1:p.Leu2035Pro
NC_000001.10:g.94466618A>G
NM_000350.2:c.6326T>C

Protein change:

L2035P

Links:

dbSNP: rs886044761

NCBI 1000 Genomes Browser:

rs886044761

Molecular consequence:

NM_000350.3:c.6326T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.6104T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001219694	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 21, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 28118664, 29555955, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001219694

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 21, 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

Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs.

Schulz HL, Grassmann F, Kellner U, Spital G, Rüther K, Jägle H, Hufendiek K, Rating P, Huchzermeyer C, Baier MJ, Weber BH, Stöhr H.

Invest Ophthalmol Vis Sci. 2017 Jan 1;58(1):394-403. doi: 10.1167/iovs.16-19936.

PubMed [citation]

PMID:: 28118664
PMCID:: PMC5270621

Clinical and genetic characteristics of 251 consecutive patients with macular and cone/cone-rod dystrophy.

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

Sci Rep. 2018 Mar 19;8(1):4824. doi: 10.1038/s41598-018-22096-0.

PubMed [citation]

PMID:: 29555955
PMCID:: PMC5859282

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001219694.5

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

Description

For these reasons, this variant has been classified as Pathogenic. 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. ClinVar contains an entry for this variant (Variation ID: 236147). This missense change has been observed in individuals with ABCA4-related retinal dystrophy (PMID: 28118664, 29555955). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2109 of the ABCA4 protein (p.Leu2109Pro).

#	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: Oct 20, 2024

ClinVar

Relating variation to medicine