NM_000350.3(ABCA4):c.6722T>C (p.Leu2241Pro) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 4, 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:: RCV001038128.8

Allele description [Variation Report for NM_000350.3(ABCA4):c.6722T>C (p.Leu2241Pro)]

NM_000350.3(ABCA4):c.6722T>C (p.Leu2241Pro)

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.6722T>C (p.Leu2241Pro)

HGVS:

NC_000001.11:g.93997868A>G
NG_009073.1:g.128282T>C
NG_009073.2:g.128280T>C
NM_000350.3:c.6722T>CMANE SELECT
NM_001425324.1:c.6500T>C
NP_000341.2:p.Leu2241Pro
NP_001412253.1:p.Leu2167Pro
NC_000001.10:g.94463424A>G
NM_000350.2:c.6722T>C

Protein change:

L2167P

Links:

dbSNP: rs1659051255

NCBI 1000 Genomes Browser:

rs1659051255

Molecular consequence:

NM_000350.3:c.6722T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001425324.1:c.6500T>C - 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
SCV001201577	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 4, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 29925512, 30563929, 33261146, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001201577

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 4, 2022)

germline

clinical testing

PubMed (4)
[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

Detailed genetic characteristics of an international large cohort of patients with Stargardt disease: ProgStar study report 8.

Fujinami K, Strauss RW, Chiang JP, Audo IS, Bernstein PS, Birch DG, Bomotti SM, Cideciyan AV, Ervin AM, Marino MJ, Sahel JA, Mohand-Said S, Sunness JS, Traboulsi EI, West S, Wojciechowski R, Zrenner E, Michaelides M, Scholl HPN; ProgStar Study Group.; ProgStar Study Group..

Br J Ophthalmol. 2019 Mar;103(3):390-397. doi: 10.1136/bjophthalmol-2018-312064. Epub 2018 Jun 20.

PubMed [citation]

PMID:: 29925512
PMCID:: PMC6579578

Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease.

Xiang Q, Cao Y, Xu H, Guo Y, Yang Z, Xu L, Yuan L, Deng H.

Biosci Rep. 2019 Jan 15;39(1). doi:pii: BSR20180872. 10.1042/BSR20180872. Print 2019 Jan 31.

PubMed [citation]

PMID:: 30563929
PMCID:: PMC6331664

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001201577.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Leu2241 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29925512; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: 836905). This missense change has been observed in individual(s) with retinitis pigmentosa and/or Stargardt disease (PMID: 30563929, 33261146). 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 2241 of the ABCA4 protein (p.Leu2241Pro).

#	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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