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NM_006343.3(MERTK):c.992_993del (p.Ser331fs) AND MERTK-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 24, 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:
RCV003413772.4

Allele description [Variation Report for NM_006343.3(MERTK):c.992_993del (p.Ser331fs)]

NM_006343.3(MERTK):c.992_993del (p.Ser331fs)

Genes:
MERTK:MER proto-oncogene, tyrosine kinase [Gene - OMIM - HGNC]
LOC112806037:Sharpr-MPRA regulatory region 3720 [Gene]
Variant type:
Deletion
Cytogenetic location:
2q13
Genomic location:
Preferred name:
NM_006343.3(MERTK):c.992_993del (p.Ser331fs)
HGVS:
  • NC_000002.12:g.111975320_111975321del
  • NG_011607.1:g.81707_81708del
  • NG_060893.1:g.229_230del
  • NM_006343.2:c.992_993delCA
  • NM_006343.3:c.992_993delMANE SELECT
  • NP_006334.2:p.Ser331fs
  • NC_000002.11:g.112732897_112732898del
  • NC_000002.11:g.112732897_112732898del
  • NC_000002.11:g.112732897_112732898delCA
Protein change:
S331fs
Links:
dbSNP: rs1573613491
NCBI 1000 Genomes Browser:
rs1573613491
Molecular consequence:
  • NM_006343.3:c.992_993del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
MERTK-related disorder
Synonyms:
MERTK-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004117835PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)		Likely pathogenic
(Nov 24, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004117835.1

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

Description

The MERTK c.992_993delCA variant is predicted to result in a frameshift and premature protein termination (p.Ser331Cysfs*5). This variant was reported homozygous in 3 siblings with autosomal recessive retinitis pigmentosa (Lukovic et al 2015. PubMed ID: 26263531). The siblings were from a consanguineous family. In vitro functional characterization showed that patient-specific retinal pigment epithelium cells exhibited defective phagocytosis, a characteristic phenotype of MERTK deficiency observed in human patients and animal models. This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Frameshift variants in MERTK are expected to be pathogenic. This variant is interpreted as pathogenic.

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

Last Updated: Sep 29, 2024