NM_017777.4(MKS1):c.1450_1453dup (p.Thr485fs) AND MKS1-related disorder

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Apr 27, 2017
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:: RCV000340753.5

Allele description [Variation Report for NM_017777.4(MKS1):c.1450_1453dup (p.Thr485fs)]

NM_017777.4(MKS1):c.1450_1453dup (p.Thr485fs)

Gene:

MKS1:MKS transition zone complex subunit 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

17q22

Genomic location:

Preferred name:

NM_017777.4(MKS1):c.1450_1453dup (p.Thr485fs)

HGVS:

NC_000017.11:g.58206504_58206507dup
NG_013020.1:g.18777_18780dup
NG_013032.1:g.18101_18104dup
NM_001321268.2:c.841_844dup
NM_001321269.2:c.1408-125_1408-122dup
NM_001330397.2:c.1274-125_1274-122dup
NM_017777.4:c.1450_1453dupMANE SELECT
NP_001308197.1:p.Thr282fs
NP_060247.2:p.Thr485fs
NP_060247.2:p.Thr485fs
LRG_687t1:c.1450_1453dup
LRG_687:g.18101_18104dup
LRG_687p1:p.Thr485fs
NC_000017.10:g.56283862_56283863insTGCC
NC_000017.10:g.56283865_56283868dup
NM_017777.3:c.1450_1453dup
NM_017777.3:c.1450_1453dupGGCA
NM_017777.4:c.1450_1453dup

Protein change:

T282fs

Links:

dbSNP: rs386834044

NCBI 1000 Genomes Browser:

rs386834044

Molecular consequence:

NM_001321268.2:c.841_844dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_017777.4:c.1450_1453dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001321269.2:c.1408-125_1408-122dup - intron variant - [Sequence Ontology: SO:0001627]
NM_001330397.2:c.1274-125_1274-122dup - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: MKS1-related disorder
Synonyms:: MKS1-Related Disorders; MKS1-related condition
Identifiers:: MedGen: CN239382

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
SCV000404278	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 09 May 2019)	Likely pathogenic (Apr 27, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 17397051, 17185389, 23351400 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000404278

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 09 May 2019)

Likely pathogenic
(Apr 27, 2017)

germline

clinical testing

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

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

Citations

PubMed

Spectrum of MKS1 and MKS3 mutations in Meckel syndrome: a genotype-phenotype correlation. Mutation in brief #960. Online.

Khaddour R, Smith U, Baala L, Martinovic J, Clavering D, Shaffiq R, Ozilou C, Cullinane A, Kyttälä M, Shalev S, Audollent S, d'Humières C, Kadhom N, Esculpavit C, Viot G, Boone C, Oien C, Encha-Razavi F, Batman PA, Bennett CP, Woods CG, Roume J, et al.

Hum Mutat. 2007 May;28(5):523-4.

PubMed [citation]

PMID:: 17397051

The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation.

Dawe HR, Smith UM, Cullinane AR, Gerrelli D, Cox P, Badano JL, Blair-Reid S, Sriram N, Katsanis N, Attie-Bitach T, Afford SC, Copp AJ, Kelly DA, Gull K, Johnson CA.

Hum Mol Genet. 2007 Jan 15;16(2):173-86. Epub 2006 Dec 21.

PubMed [citation]

PMID:: 17185389

See all PubMed Citations (3)

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000404278.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The MKS1 c.1450_1453dupGGCA (p.Thr485ArgfsTer107) variant, also known as c.1448_1451dupCAGG, results in a frameshift and is predicted to cause an elongation of the protein. Across a selection of available literature, the p.Thr485ArgfsTer107 variant was identified in a homozygous state in four individuals with Meckel syndrome from consanguineous families of Pakistani origin (Dawe et al. 2007; Khaddour et al. 2007; Szymanska et al. 2012). The p.Thr485ArgfsTer107 variant has not been reported in any cases of Bardet-Biedl syndrome. The variant was absent from 96 healthy controls but is reported at a frequency of 0.00067 in the South Asian population of the Exome Aggregation Consortium. Dawe et al. (2007) conducted immunohistochemistry staining in kidney tissue from an affected individual carrying the p.Thr485ArgfsTer107 variant and demonstrated a lack of MKS1 protein compared to age-matched control tissue. Based on the evidence from the literature and potential impact of frameshift variants, the p.Thr485ArgfsTer107 variant is classified as likely pathogenic for MKS1-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

#	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

ClinVar

Relating variation to medicine