VCV000384332.2 - ClinVar

NM_018896.5(CACNA1G):c.262A>G (p.Met88Val)

Germline

Classification

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)

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

criteria provided, single submitter

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_018896.5(CACNA1G):c.262A>G (p.Met88Val)

Variation ID: 384332 Accession: VCV000384332.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 17q21.33 17: 50568889 (GRCh38) [ NCBI UCSC ] 17: 48646250 (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	Mar 8, 2017	Mar 8, 2017	Mar 8, 2016

HGVS

Nucleotide	Protein	Molecular consequence
NM_018896.5:c.262A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_061496.2:p.Met88Val	missense
NM_001256324.2:c.262A>G	NP_001243253.1:p.Met88Val	missense
NM_001256325.2:c.262A>G	NP_001243254.1:p.Met88Val	missense
NM_001256326.2:c.262A>G	NP_001243255.1:p.Met88Val	missense
NM_001256327.2:c.262A>G	NP_001243256.1:p.Met88Val	missense
NM_001256328.2:c.262A>G	NP_001243257.1:p.Met88Val	missense
NM_001256329.2:c.262A>G	NP_001243258.1:p.Met88Val	missense
NM_001256330.2:c.262A>G	NP_001243259.1:p.Met88Val	missense
NM_001256331.2:c.262A>G	NP_001243260.1:p.Met88Val	missense
NM_001256332.2:c.262A>G	NP_001243261.1:p.Met88Val	missense
NM_001256333.2:c.262A>G	NP_001243262.1:p.Met88Val	missense
NM_001256334.2:c.262A>G	NP_001243263.1:p.Met88Val	missense
NM_001256359.2:c.262A>G	NP_001243288.1:p.Met88Val	missense
NM_001256360.2:c.262A>G	NP_001243289.1:p.Met88Val	missense
NM_001256361.2:c.262A>G	NP_001243290.1:p.Met88Val	missense
NM_198376.3:c.262A>G	NP_938190.1:p.Met88Val	missense
NM_198377.3:c.262A>G	NP_938191.2:p.Met88Val	missense
NM_198378.3:c.262A>G	NP_938192.1:p.Met88Val	missense
NM_198379.3:c.262A>G	NP_938193.1:p.Met88Val	missense
NM_198380.3:c.262A>G	NP_938194.1:p.Met88Val	missense
NM_198382.3:c.262A>G	NP_938196.1:p.Met88Val	missense
NM_198383.3:c.262A>G	NP_938197.1:p.Met88Val	missense
NM_198384.3:c.262A>G	NP_938198.1:p.Met88Val	missense
NM_198385.3:c.262A>G	NP_938199.1:p.Met88Val	missense
NM_198386.3:c.262A>G	NP_938200.1:p.Met88Val	missense
NM_198387.3:c.262A>G	NP_938201.1:p.Met88Val	missense
NM_198388.3:c.262A>G	NP_938202.1:p.Met88Val	missense
NM_198396.3:c.262A>G	NP_938406.1:p.Met88Val	missense
NR_046054.2:n.1007A>G		non-coding transcript variant
NR_046055.2:n.1007A>G		non-coding transcript variant
NR_046056.2:n.1007A>G		non-coding transcript variant
NR_046057.2:n.1007A>G		non-coding transcript variant
NR_046058.2:n.1007A>G		non-coding transcript variant
NC_000017.11:g.50568889A>G
NC_000017.10:g.48646250A>G
NG_032024.1:g.12822A>G

... more HGVS ... less HGVS

Protein change

M88V

Other names

Canonical SPDI

NC_000017.11:50568888:A:G

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The 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.

The Genome Aggregation Database (gnomAD) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00001

1000 Genomes Project 30x 0.00016

Links

ClinGen: CA16607378 dbSNP: rs1057521926 VarSome

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
Gene	OMIM	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.
CACNA1G		-	-	GRCh38 GRCh37	1081	1124

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.
not provided	Uncertain significance (1)	criteria provided, single submitter	Mar 8, 2016	RCV000436422.1

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 (Mar 08, 2016)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000525095.4 First in ClinVar: Mar 08, 2017 Last updated: Mar 08, 2017	Comment: The M88V variant in the CACNA1G gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The … (more) The M88V variant in the CACNA1G gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M88V variant was not observed in approximately 6400 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 M88V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret M88V as a variant of uncertain significance. (less)

Comment:

The M88V variant in the CACNA1G gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M88V variant was not observed in approximately 6400 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 M88V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. However, in silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret M88V as a variant of uncertain significance.

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:

Citations for germline classification of this variant

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 rs1057521926 ...

These 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 Dec 25, 2023

ClinVar Genomic variation as it relates to human health

NM_018896.5(CACNA1G):c.262A>G (p.Met88Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1057521926 ...