The c.4281A>C(p.Lys1427Asn) variant in the MAP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Lys1427Asn variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Lys at position 1427 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Lys1427Asn in MAP2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance .
ClinVar Genomic variation as it relates to human health
NM_001375505.1(MAP2):c.4281A>C (p.Lys1427Asn)
Germline
Classification
Help
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
(1)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Uncertain significance
1
criteria provided, single submitter
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_001375505.1(MAP2):c.4281A>C (p.Lys1427Asn)
Variation ID: 1878555 Accession: VCV001878555.1
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 2q34 2: 209696642 (GRCh38) [ NCBI UCSC ] 2: 210561366 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jan 21, 2023 Jan 21, 2023 - HGVS
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... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001375505.1:c.4281A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001362434.1:p.Lys1427Asn missense NM_001039538.2:c.455-3635A>C intron variant NM_001363910.2:c.4269A>C NP_001350839.1:p.Lys1423Asn missense NM_001363911.2:c.4269A>C NP_001350840.1:p.Lys1423Asn missense NM_001363913.2:c.455-3635A>C intron variant NM_001375474.1:c.455-3635A>C intron variant NM_001375493.1:c.455-3635A>C intron variant NM_001375494.1:c.455-3635A>C intron variant NM_001375495.1:c.555A>C NP_001362424.1:p.Lys185Asn missense NM_001375496.1:c.455-3638A>C intron variant NM_001375497.1:c.452-3635A>C intron variant NM_001375498.1:c.552A>C NP_001362427.1:p.Lys184Asn missense NM_001375499.1:c.455-3635A>C intron variant NM_001375500.1:c.4269A>C NP_001362429.1:p.Lys1423Asn missense NM_001375501.1:c.4527A>C NP_001362430.1:p.Lys1509Asn missense NM_001375502.1:c.4278A>C NP_001362431.1:p.Lys1426Asn missense NM_001375503.1:c.4512A>C NP_001362432.1:p.Lys1504Asn missense NM_001375504.1:c.4281A>C NP_001362433.1:p.Lys1427Asn missense NM_001375506.1:c.4281A>C NP_001362435.1:p.Lys1427Asn missense NM_001375507.1:c.4269A>C NP_001362436.1:p.Lys1423Asn missense NM_001375508.1:c.455-3635A>C intron variant NM_001375509.1:c.545-275A>C intron variant NM_001375510.1:c.555A>C NP_001362439.1:p.Lys185Asn missense NM_001375526.1:c.4281A>C NP_001362455.1:p.Lys1427Asn missense NM_001375527.1:c.4281A>C NP_001362456.1:p.Lys1427Asn missense NM_001375528.1:c.4269A>C NP_001362457.1:p.Lys1423Asn missense NM_001375529.1:c.452-3635A>C intron variant NM_001375530.1:c.455-3638A>C intron variant NM_001375531.1:c.4527A>C NP_001362460.1:p.Lys1509Asn missense NM_001375532.1:c.455-3638A>C intron variant NM_001375533.1:c.452-3635A>C intron variant NM_001375534.1:c.4281A>C NP_001362463.1:p.Lys1427Asn missense NM_001375535.1:c.698-3635A>C intron variant NM_001375536.1:c.555A>C NP_001362465.1:p.Lys185Asn missense NM_001375537.1:c.4527A>C NP_001362466.1:p.Lys1509Asn missense NM_001375538.1:c.555A>C NP_001362467.1:p.Lys185Asn missense NM_001375539.1:c.4515A>C NP_001362468.1:p.Lys1505Asn missense NM_001375540.1:c.552A>C NP_001362469.1:p.Lys184Asn missense NM_001375541.1:c.455-275A>C intron variant NM_001375542.1:c.452-3638A>C intron variant NM_001375543.1:c.4281A>C NP_001362472.1:p.Lys1427Asn missense NM_001375544.1:c.4278A>C NP_001362473.1:p.Lys1426Asn missense NM_001375545.1:c.4269A>C NP_001362474.1:p.Lys1423Asn missense NM_001375546.1:c.4269A>C NP_001362475.1:p.Lys1423Asn missense NM_001375548.1:c.4266A>C NP_001362477.1:p.Lys1422Asn missense NM_001375551.1:c.3807A>C NP_001362480.1:p.Lys1269Asn missense NM_001375552.1:c.3807A>C NP_001362481.1:p.Lys1269Asn missense NM_001375553.1:c.84A>C NP_001362482.1:p.Lys28Asn missense NM_001375554.1:c.84A>C NP_001362483.1:p.Lys28Asn missense NM_001375555.1:c.3807A>C NP_001362484.1:p.Lys1269Asn missense NM_001375556.1:c.3807A>C NP_001362485.1:p.Lys1269Asn missense NM_001375557.1:c.3807A>C NP_001362486.1:p.Lys1269Asn missense NM_001375558.1:c.3807A>C NP_001362487.1:p.Lys1269Asn missense NM_001375559.1:c.3807A>C NP_001362488.1:p.Lys1269Asn missense NM_001375583.1:c.455-3635A>C intron variant NM_002374.4:c.4281A>C NP_002365.3:p.Lys1427Asn missense NM_031845.3:c.455-3635A>C intron variant NM_031847.3:c.455-3635A>C intron variant NC_000002.12:g.209696642A>C NC_000002.11:g.210561366A>C NG_052836.1:g.277596A>C - Protein change
- K1269N, K1422N, K1423N, K1426N, K1427N, K1504N, K1505N, K1509N, K184N, K185N, K28N
- Other names
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- Canonical SPDI
- NC_000002.12:209696641:A:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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| MAP2 | - | - |
GRCh38 GRCh37 |
120 | 146 | |
Conditions - Germline
| Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
|---|---|---|---|---|
| Uncertain significance (1) |
criteria provided, single submitter
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- | RCV002510646.2 |
Submissions - Germline
| Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Uncertain significance
(-)
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criteria provided, single submitter
Method: clinical testing
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Rett syndrome
Affected status: yes
Allele origin:
germline
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Neuberg Centre For Genomic Medicine, NCGM
Accession: SCV002820145.1
First in ClinVar: Jan 21, 2023 Last updated: Jan 21, 2023 |
Comment:
The c.4281A>C(p.Lys1427Asn) variant in the MAP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The … (more)
The c.4281A>C(p.Lys1427Asn) variant in the MAP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Lys1427Asn variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Lys at position 1427 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Lys1427Asn in MAP2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance . (less)
Clinical Features:
Global developmental delay (present) , Hypotonia (present) , Myoclonus (present) , Poor head control (present) , Irritability (present) , Stridor (present) , Feeding difficulties (present) … (more)
Global developmental delay (present) , Hypotonia (present) , Myoclonus (present) , Poor head control (present) , Irritability (present) , Stridor (present) , Feeding difficulties (present) , Recurrent upper respiratory tract infections (present) , Hepatomegaly (present) , Flat occiput (present) (less)
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Comment:
Germline Functional Evidence
| There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Comment:
The c.4281A>C(p.Lys1427Asn) variant in the MAP2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The p.Lys1427Asn variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. The amino acid Lys at position 1427 is changed to a Asn changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be damaging by both SIFT and PolyPhen2. The residue is conserved across species. The amino acid change p.Lys1427Asn in MAP2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance .
Citations for germline classification of this variant
Help| There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for this variant ...
HelpRecord last updated Apr 06, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.