A heterozygous missense variation in exon 17 of the APP gene that results in the amino acid substitution of Proline for Threonine at codon 719 was detected. The observed variant c.2155A>C (p.Thr719Pro) has not been reported in the 1000 genomes and gnomAD database. The in-silico prediction of the variant are probably damaging by PolyPhen-2 and damaging by SIFT, MutationTaster2 and LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a likely pathogenic variant.
ClinVar Genomic variation as it relates to human health
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- Interpretation:
-
Likely pathogenic
- Review status:
- criteria provided, single submitter
- Submissions:
- 1
- First in ClinVar:
- Mar 5, 2022
- Most recent Submission:
- Mar 5, 2022
- Last evaluated:
- Oct 27, 2021
- Accession:
- VCV001342870.1
- Variation ID:
- 1342870
- Description:
- single nucleotide variant
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NM_000484.4(APP):c.2155A>C (p.Thr719Pro)
- Allele ID
- 1334507
- Variant type
- single nucleotide variant
- Variant length
- 1 bp
- Cytogenetic location
- 21q21.3
- Genomic location
- 21: 25891778 (GRCh38) GRCh38 UCSC
- 21: 27264090 (GRCh37) GRCh37 UCSC
- HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000484.4:c.2155A>C MANE Select NP_000475.1:p.Thr719Pro missense NM_001136016.3:c.2083A>C NP_001129488.1:p.Thr695Pro missense NM_001136129.3:c.1762A>C NP_001129601.1:p.Thr588Pro missense NM_001136130.3:c.1987A>C NP_001129602.1:p.Thr663Pro missense NM_001136131.3:c.1825A>C NP_001129603.1:p.Thr609Pro missense NM_001204301.2:c.2101A>C NP_001191230.1:p.Thr701Pro missense NM_001204302.2:c.2044A>C NP_001191231.1:p.Thr682Pro missense NM_001204303.2:c.1876A>C NP_001191232.1:p.Thr626Pro missense NM_001385253.1:c.1987A>C NP_001372182.1:p.Thr663Pro missense NM_201413.3:c.2098A>C NP_958816.1:p.Thr700Pro missense NM_201414.3:c.1930A>C NP_958817.1:p.Thr644Pro missense NC_000021.9:g.25891778T>G NC_000021.8:g.27264090T>G NG_007376.2:g.284351A>C - Protein change
- T588P, T609P, T626P, T644P, T663P, T682P, T695P, T700P, T701P, T719P
- Other names
- p.Thr719Pro
- Canonical SPDI
- NC_000021.9:25891777:T:G
- Functional consequence
- Unknown function
- Global minor allele frequency (GMAF)
- -
- Allele frequency
- -
- Links
- VarSome
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Aggregate interpretations per condition
| Interpreted condition | Interpretation | Number of submissions | Review status | Last evaluated | Variation/condition record |
|---|---|---|---|---|---|
| Likely pathogenic | 1 | criteria provided, single submitter | Oct 27, 2021 | RCV001842233.1 |
Help
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation | Variation viewer | Related variants | ||
|---|---|---|---|---|---|---|
| HI score Help | TS score Help | Within gene | All | |||
| APP | No evidence available | Some evidence for dosage pathogenicity |
GRCh38 GRCh37 |
423 | 489 | |
Submitted interpretations and evidence
Help| Interpretation (Last evaluated) |
Review status (Assertion criteria) |
Condition (Inheritance) |
Submitter | More information | |
|---|---|---|---|---|---|
|
Likely pathogenic
(Oct 27, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Alzheimer disease type 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102396.1
First in ClinVar: Mar 05, 2022 Last updated: Mar 05, 2022 |
Comment:
A heterozygous missense variation in exon 17 of the APP gene that results in the amino acid substitution of Proline for Threonine at codon 719 … (more)
A heterozygous missense variation in exon 17 of the APP gene that results in the amino acid substitution of Proline for Threonine at codon 719 was detected. The observed variant c.2155A>C (p.Thr719Pro) has not been reported in the 1000 genomes and gnomAD database. The in-silico prediction of the variant are probably damaging by PolyPhen-2 and damaging by SIFT, MutationTaster2 and LRT. The reference codon is conserved across species. In summary, the variant meets our criteria to be classified as a likely pathogenic variant. (less)
Clinical Features:
Dementia (present) , Progressive forgetfulness (present) , Behavioral abnormality (present) , Frontal lobe dementia (present)
Zygosity: 1 Single Heterozygote
Age: 40-49 years
Sex: female
Ethnicity/Population group: Hindu
Geographic origin: India
Method: DNA was used to perform targeted gene capture using a custom capture kit. Libraries were sequenced to mean > 80-100X coverage on the Illumina sequencing platform. Sequence obtained were aligned to human references genome using BWA program and analyzed using Picard and GATK-Lite toolkit to identify variants in the targeted genes relevant to clinical indication.
|
Functional evidence
Help| Functional consequence | Method | Result | Submitter | Supporting information
(See all) |
|---|---|---|---|---|
|
Unknown function
|
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics
Accession: SCV002102396.1
Submitted: (Mar 03, 2022)
|
|
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. |
Record last updated Nov 19, 2022