The D138N variant in the MAPT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D138N variant was not observed in approximately 6,500 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 D138N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D138N as a variant of uncertain significance.
ClinVar Genomic variation as it relates to human health
Help
- Interpretation:
-
Uncertain significance
- Review status:
- criteria provided, single submitter
- Submissions:
- 1
- First in ClinVar:
- Mar 8, 2017
- Most recent Submission:
- Mar 8, 2017
- Last evaluated:
- Jan 3, 2017
- Accession:
- VCV000392600.2
- Variation ID:
- 392600
- Description:
- single nucleotide variant
Help
NM_001377265.1(MAPT):c.1390G>A (p.Asp464Asn)
- Allele ID
- 375144
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 17q21.31
- Genomic location
- 17: 44064444 (GRCh37) GRCh37 UCSC
- 17: 45987078 (GRCh38) GRCh38 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001377265.1:c.1390G>A MANE Select NP_001364194.1:p.Asp464Asn missense NM_001123066.4:c.1165G>A NP_001116538.2:p.Asp389Asn missense NM_001123067.4:c.325G>A NP_001116539.1:p.Asp109Asn missense NM_001203251.2:c.325G>A NP_001190180.1:p.Asp109Asn missense NM_001203252.2:c.412G>A NP_001190181.1:p.Asp138Asn missense NM_001377266.1:c.1390G>A NP_001364195.1:p.Asp464Asn missense NM_001377267.1:c.325G>A NP_001364196.1:p.Asp109Asn missense NM_001377268.1:c.238G>A NP_001364197.1:p.Asp80Asn missense NM_005910.6:c.412G>A NP_005901.2:p.Asp138Asn missense NM_016834.5:c.238G>A NP_058518.1:p.Asp80Asn missense NM_016835.5:c.1165G>A NP_058519.3:p.Asp389Asn missense NM_016841.5:c.238G>A NP_058525.1:p.Asp80Asn missense NR_165166.1:n.475G>A NC_000017.11:g.45987078G>A NC_000017.10:g.44064444G>A NG_007398.1:g.97658G>A NG_007398.2:g.97616G>A LRG_660:g.97616G>A LRG_660t1:c.1165G>A LRG_660p1:p.Asp389Asn LRG_660t2:c.1390G>A LRG_660p2:p.Asp464Asn - Protein change
- D138N, D389N, D109N, D80N, D464N
- Other names
- -
- Canonical SPDI
- NC_000017.11:45987077:G:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- Exome Aggregation Consortium (ExAC) 0.00001
- The Genome Aggregation Database (gnomAD) 0.00001
- Trans-Omics for Precision Medicine (TOPMed) 0.00001
- The Genome Aggregation Database (gnomAD), exomes 0.00002
- Links
- ClinGen: CA8617869
- dbSNP: rs768615863
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Uncertain significance | 1 | criteria provided, single submitter | Jan 3, 2017 | RCV000443928.1 |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Uncertain significance
(Jan 03, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000535893.4
First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017 |
Comment:
The D138N variant in the MAPT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more)
The D138N variant in the MAPT gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The D138N variant was not observed in approximately 6,500 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 D138N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret D138N as a variant of uncertain significance. (less)
|
Functional evidence
Help| 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. |
Citations for this variant
Help| There are no citations in ClinVar for this variation. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs768615863...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Apr 25, 2022