NM_194456.1(KRIT1):c.301G>A (p.Gly101Arg) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely pathogenic(1);Uncertain significance(1) (Last evaluated: Jun 24, 2016)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000427958.1

Allele description [Variation Report for NM_194456.1(KRIT1):c.301G>A (p.Gly101Arg)]

NM_194456.1(KRIT1):c.301G>A (p.Gly101Arg)

Gene:
KRIT1:KRIT1 ankyrin repeat containing [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q21.2
Genomic location:
Preferred name:
NM_194456.1(KRIT1):c.301G>A (p.Gly101Arg)
HGVS:
  • NC_000007.14:g.92237721C>T
  • NG_012964.1:g.13380G>A
  • NM_001013406.2:c.301G>A
  • NM_001350669.1:c.301G>A
  • NM_001350670.1:c.301G>A
  • NM_001350671.1:c.-283G>A
  • NM_001350672.1:c.301G>A
  • NM_001350673.1:c.301G>A
  • NM_001350674.1:c.301G>A
  • NM_001350675.1:c.301G>A
  • NM_001350676.1:c.301G>A
  • NM_001350677.1:c.301G>A
  • NM_001350678.1:c.301G>A
  • NM_001350679.1:c.301G>A
  • NM_001350680.1:c.301G>A
  • NM_001350681.1:c.301G>A
  • NM_001350682.1:c.301G>A
  • NM_001350683.1:c.301G>A
  • NM_001350684.1:c.301G>A
  • NM_001350685.1:c.301G>A
  • NM_001350686.1:c.301G>A
  • NM_001350687.1:c.301G>A
  • NM_001350688.1:c.301G>A
  • NM_001350689.1:c.301G>A
  • NM_001350690.1:c.301G>A
  • NM_001350691.1:c.301G>A
  • NM_001350692.1:c.301G>A
  • NM_001350693.1:c.301G>A
  • NM_001350694.1:c.301G>A
  • NM_001350695.1:c.301G>A
  • NM_001350696.1:c.301G>A
  • NM_001350697.1:c.301G>A
  • NM_004912.4:c.301G>A
  • NM_194454.2:c.301G>A
  • NM_194455.1:c.301G>A
  • NM_194456.1:c.301G>A
  • NP_001013424.1:p.Gly101Arg
  • NP_001337598.1:p.Gly101Arg
  • NP_001337599.1:p.Gly101Arg
  • NP_001337601.1:p.Gly101Arg
  • NP_001337602.1:p.Gly101Arg
  • NP_001337603.1:p.Gly101Arg
  • NP_001337604.1:p.Gly101Arg
  • NP_001337605.1:p.Gly101Arg
  • NP_001337606.1:p.Gly101Arg
  • NP_001337607.1:p.Gly101Arg
  • NP_001337608.1:p.Gly101Arg
  • NP_001337609.1:p.Gly101Arg
  • NP_001337610.1:p.Gly101Arg
  • NP_001337611.1:p.Gly101Arg
  • NP_001337612.1:p.Gly101Arg
  • NP_001337613.1:p.Gly101Arg
  • NP_001337614.1:p.Gly101Arg
  • NP_001337615.1:p.Gly101Arg
  • NP_001337616.1:p.Gly101Arg
  • NP_001337617.1:p.Gly101Arg
  • NP_001337618.1:p.Gly101Arg
  • NP_001337619.1:p.Gly101Arg
  • NP_001337620.1:p.Gly101Arg
  • NP_001337621.1:p.Gly101Arg
  • NP_001337622.1:p.Gly101Arg
  • NP_001337623.1:p.Gly101Arg
  • NP_001337624.1:p.Gly101Arg
  • NP_001337625.1:p.Gly101Arg
  • NP_001337626.1:p.Gly101Arg
  • NP_004903.2:p.Gly101Arg
  • NP_919436.1:p.Gly101Arg
  • NP_919437.1:p.Gly101Arg
  • NP_919438.1:p.Gly101Arg
  • LRG_650t1:c.301G>A
  • LRG_650:g.13380G>A
  • LRG_650p1:p.Gly101Arg
  • NC_000007.13:g.91867035C>T
Protein change:
G101R
Links:
dbSNP: rs1057521140
NCBI 1000 Genomes Browser:
rs1057521140
Molecular consequence:
  • NM_001350671.1:c.-283G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001013406.2:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350669.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350670.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350672.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350673.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350674.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350675.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350676.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350677.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350678.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350679.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350680.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350681.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350682.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350683.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350684.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350685.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350686.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350687.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350688.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350689.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350690.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350691.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350692.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350693.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350694.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350695.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350696.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350697.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_004912.4:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_194454.2:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_194455.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_194456.1:c.301G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000521193GeneDxcriteria provided, single submitter
Likely pathogenic
(Jun 24, 2016)
germlineclinical testing

Citation Link,

SCV000853032PreventionGenetics,PreventionGeneticscriteria provided, single submitter
Uncertain significance
(Oct 8, 2013)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From GeneDx, SCV000521193.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The G101R variant has been previously published in association with cerebral cavernous malformations (CCM) (Fisher et al., 2015) with limited data to fully support pathogenicity. G101R was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The G101R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is highly conserved across species, in silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, the variant has been observed to segregate with the disease. However, G101R is located in a loop of the gene's Nudix domain with no known functional importance (Fisher et al., 2015) and similar variants in nearby residues have not been reported in association with CCM (Stenson et al., 2014). Therefore, this variant is likely pathogenic; however, the possibility it is a benign variant cannot be excluded.

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

From PreventionGenetics,PreventionGenetics, SCV000853032.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2021

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