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NM_017777.4(MKS1):c.508C>T (p.Arg170Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 29, 2023
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:
RCV001049084.5

Allele description

NM_017777.4(MKS1):c.508C>T (p.Arg170Ter)

Gene:
MKS1:MKS transition zone complex subunit 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q22
Genomic location:
Preferred name:
NM_017777.4(MKS1):c.508C>T (p.Arg170Ter)
HGVS:
  • NC_000017.11:g.58214748G>A
  • NG_013032.1:g.9858C>T
  • NM_001321268.2:c.-94-361C>T
  • NM_001321269.2:c.508C>T
  • NM_001330397.2:c.508C>T
  • NM_017777.4:c.508C>TMANE SELECT
  • NP_001308198.1:p.Arg170Ter
  • NP_001317326.1:p.Arg170Ter
  • NP_060247.2:p.Arg170Ter
  • NP_060247.2:p.Arg170Ter
  • LRG_687t1:c.508C>T
  • LRG_687:g.9858C>T
  • LRG_687p1:p.Arg170Ter
  • NC_000017.10:g.56292109G>A
  • NM_017777.3:c.508C>T
Protein change:
R170*
Links:
dbSNP: rs756853299
NCBI 1000 Genomes Browser:
rs756853299
Molecular consequence:
  • NM_001321268.2:c.-94-361C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001321269.2:c.508C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001330397.2:c.508C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_017777.4:c.508C>T - nonsense - [Sequence Ontology: SO:0001587]

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
Name:
Meckel-Gruber syndrome
Synonyms:
DYSENCEPHALIA SPLANCHNOCYSTICA; Gruber syndrome; Dysencephalia splachnocystica
Identifiers:
MONDO: MONDO:0018921; MedGen: C0265215; OMIM: PS249000

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001213118Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 29, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutation spectrum of Meckel syndrome genes: one group of syndromes or several distinct groups?

Tallila J, Salonen R, Kohlschmidt N, Peltonen L, Kestilä M.

Hum Mutat. 2009 Aug;30(8):E813-30. doi: 10.1002/humu.21057.

PubMed [citation]
PMID:
19466712
PMCID:
PMC2718326

Mutations in B9D1 and MKS1 cause mild Joubert syndrome: expanding the genetic overlap with the lethal ciliopathy Meckel syndrome.

Romani M, Micalizzi A, Kraoua I, Dotti MT, Cavallin M, Sztriha L, Ruta R, Mancini F, Mazza T, Castellana S, Hanene B, Carluccio MA, Darra F, Máté A, Zimmermann A, Gouider-Khouja N, Valente EM.

Orphanet J Rare Dis. 2014 May 5;9:72. doi: 10.1186/1750-1172-9-72.

PubMed [citation]
PMID:
24886560
PMCID:
PMC4113192
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001213118.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Arg170*) in the MKS1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MKS1 are known to be pathogenic (PMID: 19466712, 24886560, 26490104). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MKS1-related conditions. ClinVar contains an entry for this variant (Variation ID: 235405). 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.

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

Last Updated: Jun 17, 2024