NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs) AND Cerebral cavernous malformation

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Sep 28, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000816950.4

Allele description [Variation Report for NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs)]

NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs)

Gene:
KRIT1:KRIT1 ankyrin repeat containing [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
7q21.2
Genomic location:
Preferred name:
NM_194454.3(KRIT1):c.1201_1204del (p.Gln401fs)
HGVS:
  • NC_000007.14:g.92225773GTTT[1]
  • NG_012964.1:g.25324CAAA[1]
  • NM_001013406.2:c.1057_1060del
  • NM_001350669.1:c.1057_1060del
  • NM_001350670.1:c.1057_1060del
  • NM_001350671.1:c.487_490del
  • NM_001350672.1:c.1201_1204del
  • NM_001350673.1:c.1201_1204del
  • NM_001350674.1:c.1201_1204del
  • NM_001350675.1:c.1201_1204del
  • NM_001350676.1:c.1201_1204del
  • NM_001350677.1:c.1201_1204del
  • NM_001350678.1:c.1201_1204del
  • NM_001350679.1:c.1201_1204del
  • NM_001350680.1:c.1201_1204del
  • NM_001350681.1:c.1201_1204del
  • NM_001350682.1:c.1201_1204del
  • NM_001350683.1:c.1201_1204del
  • NM_001350684.1:c.1201_1204del
  • NM_001350685.1:c.1201_1204del
  • NM_001350686.1:c.1201_1204del
  • NM_001350687.1:c.1201_1204del
  • NM_001350688.1:c.1201_1204del
  • NM_001350689.1:c.1201_1204del
  • NM_001350690.1:c.1201_1204del
  • NM_001350691.1:c.1201_1204del
  • NM_001350692.1:c.1201_1204del
  • NM_001350693.1:c.1201_1204del
  • NM_001350694.1:c.1201_1204del
  • NM_001350695.1:c.1201_1204del
  • NM_001350696.1:c.1201_1204del
  • NM_001350697.1:c.1201_1204del
  • NM_004912.4:c.1201_1204del
  • NM_194454.3:c.1201_1204delMANE SELECT
  • NM_194455.1:c.1201_1204del
  • NM_194456.1:c.1201_1204del
  • NP_001013424.1:p.Gln353fs
  • NP_001337598.1:p.Gln353fs
  • NP_001337599.1:p.Gln353fs
  • NP_001337600.1:p.Gln163fs
  • NP_001337601.1:p.Gln401fs
  • NP_001337602.1:p.Gln401fs
  • NP_001337603.1:p.Gln401fs
  • NP_001337604.1:p.Gln401fs
  • NP_001337605.1:p.Gln401fs
  • NP_001337606.1:p.Gln401fs
  • NP_001337607.1:p.Gln401fs
  • NP_001337608.1:p.Gln401fs
  • NP_001337609.1:p.Gln401fs
  • NP_001337610.1:p.Gln401fs
  • NP_001337611.1:p.Gln401fs
  • NP_001337612.1:p.Gln401fs
  • NP_001337613.1:p.Gln401fs
  • NP_001337614.1:p.Gln401fs
  • NP_001337615.1:p.Gln401fs
  • NP_001337616.1:p.Gln401fs
  • NP_001337617.1:p.Gln401fs
  • NP_001337618.1:p.Gln401fs
  • NP_001337619.1:p.Gln401fs
  • NP_001337620.1:p.Gln401fs
  • NP_001337621.1:p.Gln401fs
  • NP_001337622.1:p.Gln401fs
  • NP_001337623.1:p.Gln401fs
  • NP_001337624.1:p.Gln401fs
  • NP_001337625.1:p.Gln401fs
  • NP_001337626.1:p.Gln401fs
  • NP_004903.2:p.Gln401fs
  • NP_919436.1:p.Gln401fs
  • NP_919437.1:p.Gln401fs
  • NP_919438.1:p.Gln401fs
  • LRG_650t1:c.1201_1204del
  • LRG_650:g.25324CAAA[1]
  • LRG_650p1:p.Gln401fs
  • NC_000007.13:g.91855084_91855087del
  • NC_000007.13:g.91855087GTTT[1]
  • NM_004912.3:c.1201_1204delCAAA
  • NM_194456.1:c.1201_1204delCAAA
Protein change:
Q163fs
Links:
dbSNP: rs1057517753
NCBI 1000 Genomes Browser:
rs1057517753
Molecular consequence:
  • NM_001013406.2:c.1057_1060del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350669.1:c.1057_1060del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350670.1:c.1057_1060del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350671.1:c.487_490del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350672.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350673.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350674.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350675.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350676.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350677.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350678.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350679.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350680.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350681.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350682.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350683.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350684.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350685.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350686.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350687.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350688.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350689.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350690.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350691.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350692.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350693.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350694.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350695.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350696.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001350697.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004912.4:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194454.3:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194455.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_194456.1:c.1201_1204del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Cerebral cavernous malformation (CCM)
Synonyms:
CEREBRAL CAVERNOUS MALFORMATIONS; CAVERNOUS ANGIOMA, FAMILIAL; CAVERNOUS ANGIOMATOUS MALFORMATIONS; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0000820; MedGen: C2919945; Orphanet: 221061; OMIM: 116860

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000957480Invitaecriteria provided, single submitter
Pathogenic
(Sep 28, 2019)
germlineclinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV001366349Centre for Mendelian Genomics,University Medical Centre Ljubljanacriteria provided, single submitter
Uncertain significance
(Jan 1, 2016)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod

Citations

PubMed

Identification of a Novel Deletion Mutation (c.1780delG) and a Novel Splice-Site Mutation (c.1412-1G>A) in the CCM1/KRIT1 Gene Associated with Familial Cerebral Cavernous Malformation in the Chinese Population.

Yang C, Zhao J, Wu B, Zhong H, Li Y, Xu Y.

J Mol Neurosci. 2017 Jan;61(1):8-15. doi: 10.1007/s12031-016-0836-2. Epub 2016 Sep 20.

PubMed [citation]
PMID:
27649701

Familial cerebral cavernomas due to a KRIT1 mutation presenting with epilepsy.

Rajakulendran S, Andole S, Kennedy A.

BMJ Case Rep. 2011 Mar 24;2011. doi:pii: bcr0120113784. 10.1136/bcr.01.2011.3784.

PubMed [citation]
PMID:
22699465
PMCID:
PMC3070345
See all PubMed Citations (10)

Details of each submission

From Invitae, SCV000957480.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (9)

Description

This sequence change creates a premature translational stop signal (p.Gln401Thrfs*10) in the KRIT1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with cerebral cavernous malformations (PMID: 27649701,22699465, 20884211, 2359550, 18300272, Invitae). ClinVar contains an entry for this variant (Variation ID: 372398). This variant is also known as c.1197_1200delCAAA in the literature. Loss-of-function variants in KRIT1 are known to be pathogenic (PMID: 10508515, 11222804, 12404106). For these reasons, this variant has been classified as Pathogenic.

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

From Centre for Mendelian Genomics,University Medical Centre Ljubljana, SCV001366349.2

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

Description

This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PM2,PP4,PP5.

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

Last Updated: Jun 23, 2021

Support Center