The variant has been previously reported as de novo in a similarly affected individual (PMID: 27631024, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PIK3CA related disorder (PMID:27631024, PS1_P). A different missense change at the same codon (p.Pro449Ser) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000864863, PM5_M). A missense variant is a common mechanism associated with Megalencephaly-capillary malformation-polymicrogyria syndrome (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Pathogenic/Likely pathogenic
- Review status:
- criteria provided, multiple submitters, no conflicts
- Submissions:
- 2
- First in ClinVar:
- Jan 15, 2022
- Most recent Submission:
- Feb 11, 2022
- Last evaluated:
- Jan 3, 2022
- Accession:
- VCV001333250.5
- Variation ID:
- 1333250
- Description:
- single nucleotide variant
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NM_006218.4(PIK3CA):c.1345C>A (p.Pro449Thr)
- Allele ID
- 1324025
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 3q26.32
- Genomic location
- 3: 179210279 (GRCh38) GRCh38 UCSC
- 3: 178928067 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_006218.4:c.1345C>A MANE Select NP_006209.2:p.Pro449Thr missense NC_000003.12:g.179210279C>A NC_000003.11:g.178928067C>A NG_012113.2:g.66757C>A LRG_310:g.66757C>A - Protein change
- P449T
- Other names
- -
- Canonical SPDI
- NC_000003.12:179210278:C:A
- Functional consequence
- -
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- VarSome
Help
Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Pathogenic/Likely pathogenic | 2 | criteria provided, multiple submitters, no conflicts | Jan 3, 2022 | RCV001807938.5 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| PIK3CA | No evidence available | No evidence available |
GRCh38 GRCh37 |
1072 | 1106 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Pathogenic
(Jan 03, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Megalencephaly-capillary malformation-polymicrogyria syndrome
Affected status: yes
Allele origin:
germline
|
3billion
Accession: SCV002058239.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27631024, PS2_S). Same nucleotide change resulting in same amino acid … (more)
The variant has been previously reported as de novo in a similarly affected individual (PMID: 27631024, PS2_S). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with PIK3CA related disorder (PMID:27631024, PS1_P). A different missense change at the same codon (p.Pro449Ser) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000864863, PM5_M). A missense variant is a common mechanism associated with Megalencephaly-capillary malformation-polymicrogyria syndrome (PP2_P). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Capillary malformation (present) , Hemihypertrophy (present) , Macrocephaly (present)
Zygosity: 1 Single Heterozygote
|
|
|
Likely pathogenic
(Jul 15, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Megalencephaly-capillary malformation-polymicrogyria syndrome
Affected status: yes
Allele origin:
germline
|
Greenwood Genetic Center Diagnostic Laboratories,Greenwood Genetic Center
Accession: SCV002061495.2
First in ClinVar: Jan 22, 2022 Last updated: Feb 11, 2022 |
Comment:
PM6, PM1, PM2, PP2, PP3, PS4_Moderate
|
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| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| PIK3CA-associated developmental disorders exhibit distinct classes of mutations with variable expression and tissue distribution. | Mirzaa G | JCI insight | 2016 | PMID: 27631024 |
| PMID:27631024 | - | - | - | - |
Record last updated Apr 30, 2023