NM_006343.3(MERTK):c.1450G>A (p.Gly484Ser) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 1, 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:: RCV002515922.3

Allele description [Variation Report for NM_006343.3(MERTK):c.1450G>A (p.Gly484Ser)]

NM_006343.3(MERTK):c.1450G>A (p.Gly484Ser)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

2q13

Genomic location:

Preferred name:

NM_006343.3(MERTK):c.1450G>A (p.Gly484Ser)

HGVS:

NC_000002.12:g.111994404G>A
NG_011607.1:g.100791G>A
NM_006343.3:c.1450G>AMANE SELECT
NP_006334.2:p.Gly484Ser
NC_000002.11:g.112751981G>A
NM_006343.2:c.1450G>A

Protein change:

G484S

Links:

dbSNP: rs527236084

NCBI 1000 Genomes Browser:

rs527236084

Molecular consequence:

NM_006343.3:c.1450G>A - 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
SCV003524731	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 1, 2022)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 24265693, 25324289, 32036094, 33353011, 17576681, 9536098, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003524731

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 1, 2022)

germline

clinical testing

PubMed (7)
[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

Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.

Eisenberger T, Neuhaus C, Khan AO, Decker C, Preising MN, Friedburg C, Bieg A, Gliem M, Charbel Issa P, Holz FG, Baig SM, Hellenbroich Y, Galvez A, Platzer K, Wollnik B, Laddach N, Ghaffari SR, Rafati M, Botzenhart E, Tinschert S, Börger D, Bohring A, et al.

PLoS One. 2013;8(11):e78496. doi: 10.1371/journal.pone.0078496. Erratum in: PLoS One. 2014;9(11):e108840.

PubMed [citation]

PMID:: 24265693
PMCID:: PMC3827063

Comprehensive molecular diagnosis of a large cohort of Japanese retinitis pigmentosa and Usher syndrome patients by next-generation sequencing.

Oishi M, Oishi A, Gotoh N, Ogino K, Higasa K, Iida K, Makiyama Y, Morooka S, Matsuda F, Yoshimura N.

Invest Ophthalmol Vis Sci. 2014 Oct 16;55(11):7369-75. doi: 10.1167/iovs.14-15458.

PubMed [citation]

PMID:: 25324289

See all PubMed Citations (7)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003524731.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

This sequence change affects codon 484 of the MERTK mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the MERTK protein. This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon. This variant is present in population databases (rs527236084, gnomAD 0.01%). This variant has been observed in individual(s) with inherited retinal dystrophy (PMID: 24265693, 25324289, 32036094, 33353011). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 143138). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

#	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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