NM_006343.3(MERTK):c.2070_2074del (p.Gly691fs) AND Retinitis pigmentosa 38

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 9, 2019
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:: RCV001001159.8

Allele description [Variation Report for NM_006343.3(MERTK):c.2070_2074del (p.Gly691fs)]

NM_006343.3(MERTK):c.2070_2074del (p.Gly691fs)

Gene:

MERTK:MER proto-oncogene, tyrosine kinase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

2q13

Genomic location:

Preferred name:

NM_006343.3(MERTK):c.2070_2074del (p.Gly691fs)

HGVS:

NC_000002.12:g.112010057_112010061del
NG_011607.1:g.116444_116448del
NM_006343.3:c.2070_2074delMANE SELECT
NP_006334.2:p.Gly691fs
NC_000002.11:g.112767634_112767638del
NC_000002.11:g.112767634_112767638delAGGAC

Protein change:

G691fs

Links:

OMIM: 604705.0001; dbSNP: rs1573638426

NCBI 1000 Genomes Browser:

rs1573638426

Molecular consequence:

NM_006343.3:c.2070_2074del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Retinitis pigmentosa 38 (RP38)
Synonyms:: ROD-CONE DYSTROPHY, CHILDHOOD-ONSET
Identifiers:: MONDO: MONDO:0013469; MedGen: C3151228; Orphanet: 791; OMIM: 613862

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
SCV000025913	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV001158308	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	Pathogenic (Apr 9, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000025913

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 2000)

germline

literature only

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

SCV001158308

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)

Pathogenic
(Apr 9, 2019)

germline

clinical testing

Citation Link

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	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa.

Gal A, Li Y, Thompson DA, Weir J, Orth U, Jacobson SG, Apfelstedt-Sylla E, Vollrath D.

Nat Genet. 2000 Nov;26(3):270-1.

PubMed [citation]

PMID:: 11062461

Details of each submission

From OMIM, SCV000025913.2

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

Description

In a sample from a 45-year-old man with retinitis pigmentosa (RP38; 613862) who was the offspring of a consanguineous union, Gal et al. (2000) found an apparently homozygous 5-bp deletion in exon 15 (2070delAGGAC) of the MERTK gene. He had onset of night blindness and poor vision in early childhood and at the time of study had only a small central island of remaining vision. Two children were heterozygous. The mutation resulted in a frameshift after codon 690, predicting inclusion of 41 MERTK-unrelated amino acid residues before premature termination. This predicted mutant protein would lack nearly one-third of the wildtype residues, including most of the conserved tyrosine kinase domain.

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

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001158308.1

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

Description

The MERTK c.2070_2074delAGGAC; p.Gly691fs variant is reported in the literature in the homozygous state in an individual affected with retinitis pigmentosa (Gal 2000). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. This variant causes a frameshift by deleting five nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Further, MERTK loss-of-function is an established mechanism of disease, and truncating variants downstream of p.Gly691fs have been described in individuals with retinal dystrophies and are considered disease-causing (Audo 2018, Patel 2016). Based on available information, this variant is considered to be pathogenic. References: Audo I et al. MERTK mutation update in inherited retinal diseases. Hum Mutat. 2018 Jul;39(7):887-913. Gal A et al. Mutations in MERTK, the human orthologue of the RCS rat retinal dystrophy gene, cause retinitis pigmentosa. Nat Genet. 2000 Nov;26(3):270-1. Patel N et al. Expanding the clinical, allelic, and locus heterogeneity of retinal dystrophies. Genet Med. 2016 Jun;18(6):554-62.

#	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 23, 2024

ClinVar

Relating variation to medicine