NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu) AND Leber congenital amaurosis 4

Germline classification:: Conflicting classifications of pathogenicity (3 submissions)
Last evaluated:: Feb 3, 2025
Review status:: criteria provided, conflicting classifications

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:: RCV000055942.27

Allele description [Variation Report for NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu)]

NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu)

Gene:

AIPL1:AIP like 1 HSP90 co-chaperone [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.2

Genomic location:

Preferred name:

NM_014336.5(AIPL1):c.905G>T (p.Arg302Leu)

HGVS:

NC_000017.11:g.6425710C>A
NG_008474.1:g.14490G>T
NM_001033054.3:c.716G>T
NM_001033055.3:c.725G>T
NM_001285399.3:c.869G>T
NM_001285400.3:c.839G>T
NM_001285401.3:c.833G>T
NM_001285402.2:c.788G>T
NM_001285403.4:c.*876G>T
NM_014336.5:c.905G>TMANE SELECT
NP_001028226.1:p.Arg239Leu
NP_001028227.1:p.Arg242Leu
NP_001272328.1:p.Arg290Leu
NP_001272329.1:p.Arg280Leu
NP_001272330.1:p.Arg278Leu
NP_001272331.1:p.Arg263Leu
NP_055151.3:p.Arg302Leu
NC_000017.10:g.6329030C>A
NM_014336.3:c.905G>T
NM_014336.4:c.905G>T
Q9NZN9:p.Arg302Leu

Protein change:

R239L

Links:

UniProtKB: Q9NZN9#VAR_067166; dbSNP: rs62637015

NCBI 1000 Genomes Browser:

rs62637015

Molecular consequence:

NM_001285403.4:c.*876G>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001033054.3:c.716G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001033055.3:c.725G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285399.3:c.869G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285400.3:c.839G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285401.3:c.833G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001285402.2:c.788G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_014336.5:c.905G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Leber congenital amaurosis 4 (LCA4)
Identifiers:: MONDO: MONDO:0011458; MedGen: C1858386; OMIM: 604393

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
SCV000086967	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (1) [See all records that cite this PMID]
SCV000405573	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Mar 6, 2018)	germline	clinical testing	Citation Link,
SCV001021769	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Feb 3, 2025)	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

SCV000086967

GeneReviews

no classification provided

not provided

unknown

literature only

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

SCV000405573

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Mar 6, 2018)

germline

clinical testing

Citation Link,

SCV001021769

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Feb 3, 2025)

germline

clinical testing

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

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
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Leber Congenital Amaurosis – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY..

Weleber RG, Francis PJ, Trzupek KM, Beattie C.

2004 Jul 7 [updated 2013 May 2]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.

PubMed [citation]

PMID:: 20301475

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneReviews, SCV000086967.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

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

From Illumina Laboratory Services, Illumina, SCV000405573.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV001021769.7

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 29, 2025

ClinVar

Relating variation to medicine