The c.1918A>G (p.K640E) alteration is located in exon 25 (coding exon 25) of the CAST gene. This alteration results from a A to G substitution at nucleotide position 1918, causing the lysine (K) at amino acid position 640 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ClinVar Genomic variation as it relates to human health
NM_001750.7(CAST):c.2041A>G (p.Lys681Glu)
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
-
NM_001750.7(CAST):c.2041A>G (p.Lys681Glu)
Variation ID: 2488423 Accession: VCV002488423.2
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 5q15 5: 96766056 (GRCh38) [ NCBI UCSC ] 5: 96101760 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Apr 15, 2023 May 1, 2024 Feb 23, 2023 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_001750.7:c.2041A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_001741.4:p.Lys681Glu missense NM_001042440.5:c.1918A>G NP_001035905.1:p.Lys640Glu missense NM_001042441.3:c.1984A>G NP_001035906.1:p.Lys662Glu missense NM_001042442.3:c.1975A>G NP_001035907.1:p.Lys659Glu missense NM_001042443.3:c.1792A>G NP_001035908.1:p.Lys598Glu missense NM_001042444.3:c.1669A>G NP_001035909.1:p.Lys557Glu missense NM_001042445.3:c.1687A>G NP_001035910.1:p.Lys563Glu missense NM_001042446.3:c.1630A>G NP_001035911.1:p.Lys544Glu missense NM_001190442.2:c.1753A>G NP_001177371.1:p.Lys585Glu missense NM_001284212.4:c.1666A>G NP_001271141.1:p.Lys556Glu missense NM_001284213.4:c.1576A>G NP_001271142.1:p.Lys526Glu missense NM_001330626.2:c.1945A>G NP_001317555.1:p.Lys649Glu missense NM_001330627.2:c.1915A>G NP_001317556.1:p.Lys639Glu missense NM_001330628.2:c.1873A>G NP_001317557.1:p.Lys625Glu missense NM_001330629.2:c.1957A>G NP_001317558.1:p.Lys653Glu missense NM_001330630.2:c.1627A>G NP_001317559.1:p.Lys543Glu missense NM_001330631.2:c.1753A>G NP_001317560.1:p.Lys585Glu missense NM_001330632.2:c.1723A>G NP_001317561.1:p.Lys575Glu missense NM_001330633.2:c.1735A>G NP_001317562.1:p.Lys579Glu missense NM_001330634.2:c.1696A>G NP_001317563.1:p.Lys566Glu missense NM_001349244.2:c.2819-2828T>C intron variant NM_001375317.1:c.1930A>G NP_001362246.1:p.Lys644Glu missense NM_001423250.1:c.1792A>G NP_001410179.1:p.Lys598Glu missense NM_001423251.1:c.1753A>G NP_001410180.1:p.Lys585Glu missense NM_001423252.1:c.1753A>G NP_001410181.1:p.Lys585Glu missense NM_001423253.1:c.1726A>G NP_001410182.1:p.Lys576Glu missense NM_001423254.1:c.1726A>G NP_001410183.1:p.Lys576Glu missense NM_001423255.1:c.1687A>G NP_001410184.1:p.Lys563Glu missense NM_001423256.1:c.1687A>G NP_001410185.1:p.Lys563Glu missense NM_001423257.1:c.1687A>G NP_001410186.1:p.Lys563Glu missense NM_001423258.1:c.1687A>G NP_001410187.1:p.Lys563Glu missense NM_001423259.1:c.1684A>G NP_001410188.1:p.Lys562Glu missense NM_001423260.1:c.1630A>G NP_001410189.1:p.Lys544Glu missense NM_016442.5:c.2819-2828T>C intron variant NM_173060.5:c.1726A>G NP_775083.1:p.Lys576Glu missense NR_104285.2:n.983A>G non-coding transcript variant NC_000005.10:g.96766056A>G NC_000005.9:g.96101760A>G NG_027839.2:g.174928T>C NG_029490.2:g.109020A>G - Protein change
- K544E, K681E, K556E, K575E, K576E, K585E, K625E, K639E, K644E, K543E, K579E, K598E, K526E, K557E, K563E, K566E, K640E, K649E, K653E, K659E, K662E, K562E
- Other names
- -
- Canonical SPDI
- NC_000005.10:96766055:A:G
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
- -
- 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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| CAST | - | - |
GRCh38 GRCh37 |
146 | 641 | |
| ERAP1 | - | - |
GRCh38 GRCh37 |
111 | 268 | |
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
|
Feb 23, 2023 | RCV003200573.9 |
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. |
|
|---|---|---|---|---|---|
|
Uncertain significance
(Feb 23, 2023)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV003904771.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The c.1918A>G (p.K640E) alteration is located in exon 25 (coding exon 25) of the CAST gene. This alteration results from a A to G substitution … (more)
The c.1918A>G (p.K640E) alteration is located in exon 25 (coding exon 25) of the CAST gene. This alteration results from a A to G substitution at nucleotide position 1918, causing the lysine (K) at amino acid position 640 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
|
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.1918A>G (p.K640E) alteration is located in exon 25 (coding exon 25) of the CAST gene. This alteration results from a A to G substitution at nucleotide position 1918, causing the lysine (K) at amino acid position 640 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
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 Nov 10, 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.