NM_017777.3(MKS1):c.508C>T (p.Arg170Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Feb 14, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001049084.2

Allele description [Variation Report for NM_017777.3(MKS1):c.508C>T (p.Arg170Ter)]

NM_017777.3(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_017777.3(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_017777.3:c.508C>T
  • NP_001308198.1:p.Arg170Ter
  • NP_001317326.1:p.Arg170Ter
  • NP_060247.2:p.Arg170Ter
  • LRG_687t1:c.508C>T
  • LRG_687t2:c.478C>T
  • LRG_687:g.9858C>T
  • LRG_687p1:p.Arg170Ter
  • LRG_687p2:p.Arg160Ter
  • NC_000017.10:g.56292109G>A
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_017777.3:c.508C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Joubert syndrome (JBTS)
Synonyms:
CEREBELLOPARENCHYMAL DISORDER IV; Cerebelloparenchymal disorder 4; Cerebellar vermis agenesis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0018772; MedGen: C0431399; Orphanet: 475; OMIM: PS213300; Human Phenotype Ontology: HP:0002335
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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001213118Invitaecriteria provided, single submitter
Pathogenic
(Feb 14, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001213118.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

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. This variant is present in population databases (rs756853299, ExAC 0.007%). This variant has not been reported in the literature in individuals 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 create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Loss-of-function variants in MKS1 are known to be pathogenic (PMID: 17397051). 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: Aug 11, 2021

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