NM_017777.4(MKS1):c.1450_1453dup (p.Thr485fs) AND Familial aplasia of the vermis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 8, 2016
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:: RCV000230084.2

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:: Familial aplasia of the vermis
Synonyms:: CEREBELLOPARENCHYMAL DISORDER IV; Joubert syndrome; Cerebelloparenchymal disorder 4; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000290334	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 8, 2016)	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

SCV000290334

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 8, 2016)

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

Citations

PubMed

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000290334.2

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

Description

This sequence change inserts 4 nucleotides in exon 16 of the MKS1 mRNA (c.1450_1453dupGGCA), causing a frameshift at codon 485. This creates a premature translational stop signal (p.Thr485Argfs*107) and is expected to result in an absent or disrupted protein product. Truncating variants in MKS1 are known to be pathogenic. This particular truncation has been reported in the homozygous state from an individual affected with Meckel Gruber syndrome in the literature (PMID: 17397051, 17185389). This variant is also known as c.1448_1451dupCAGG; p.G484fsX108 in the literature. 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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