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NM_000350.3(ABCA4):c.1919C>A (p.Pro640His) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 13, 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:
RCV003683872.2

Allele description [Variation Report for NM_000350.3(ABCA4):c.1919C>A (p.Pro640His)]

NM_000350.3(ABCA4):c.1919C>A (p.Pro640His)

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.1919C>A (p.Pro640His)
HGVS:
  • NC_000001.11:g.94062595G>T
  • NG_009073.2:g.63553C>A
  • NM_000350.3:c.1919C>AMANE SELECT
  • NM_001425324.1:c.1919C>A
  • NP_000341.2:p.Pro640His
  • NP_001412253.1:p.Pro640His
  • NC_000001.10:g.94528151G>T
  • NG_009073.1:g.63555C>A
Protein change:
P640H
Molecular consequence:
  • NM_000350.3:c.1919C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001425324.1:c.1919C>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004425335Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Jan 13, 2023)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Deducing the pathogenic contribution of recessive ABCA4 alleles in an outbred population.

Schindler EI, Nylen EL, Ko AC, Affatigato LM, Heggen AC, Wang K, Sheffield VC, Stone EM.

Hum Mol Genet. 2010 Oct 1;19(19):3693-701. doi: 10.1093/hmg/ddq284. Epub 2010 Jul 20.

PubMed [citation]
PMID:
20647261
PMCID:
PMC2935854

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004425335.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant is present in population databases (rs760790294, gnomAD 0.003%). 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. This variant disrupts the p.Pro640 amino acid residue in ABCA4. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20647261, 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. This variant has not been reported in the literature in individuals affected with ABCA4-related conditions. This sequence change replaces proline, which is neutral and non-polar, with histidine, which is basic and polar, at codon 640 of the ABCA4 protein (p.Pro640His).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024