VCV000545681.2 - ClinVar

NM_000701.8(ATP1A1):c.2432A>C (p.Asp811Ala)

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.

(2)

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.

Conflicting classifications of pathogenicity
Pathogenic(1); Uncertain significance(1)

no assertion criteria provided

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000701.8(ATP1A1):c.2432A>C (p.Asp811Ala)

Variation ID: 545681 Accession: VCV000545681.2

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p13.1 1: 116399068 (GRCh38) [ NCBI UCSC ] 1: 116941690 (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	Jul 1, 2018	Jul 16, 2023	Jun 28, 2018

HGVS

Nucleotide	Protein	Molecular consequence
NM_000701.8:c.2432A>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000692.2:p.Asp811Ala	missense
NM_001160233.1:c.2432A>C
NM_001160233.2:c.2432A>C	NP_001153705.1:p.Asp811Ala	missense
NM_001160234.2:c.2339A>C	NP_001153706.1:p.Asp780Ala	missense
NR_027645.1:n.600T>G		non-coding transcript variant
NC_000001.11:g.116399068A>C
NC_000001.10:g.116941690A>C
NG_047036.1:g.31884A>C

... more HGVS ... less HGVS

Protein change

D811A, D780A

Other names

Canonical SPDI

NC_000001.11:116399067:A:C

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.

Links

OMIM: 182310.0005 dbSNP: rs1553192783 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.
ATP1A1		-	-	GRCh38 GRCh37	310	738
ATP1A1-AS1		-	-	GRCh38	-	412

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.
Charcot-marie-tooth disease, axonal, type 2DD	Pathogenic (1)	no assertion criteria provided	Jun 28, 2018	RCV000656716.1
Charcot-Marie-Tooth disease type 2A2	Uncertain significance (1)	no assertion criteria provided	Oct 7, 2017	RCV003311874.2

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.
Pathogenic (Jun 28, 2018)	no assertion criteria provided Method: literature only	CHARCOT-MARIE-TOOTH DISEASE, AXONAL, TYPE 2DD Affected status: not provided Allele origin: germline	OMIM Accession: SCV000778856.1 First in ClinVar: Jul 01, 2018 Last updated: Jul 01, 2018	Publications: PubMed (1) PubMed: 29499166 Comment on evidence: In a 33-year-old Korean man (family 7) with autosomal dominant axonal Charcot-Marie-Tooth disease type 2DD (CMT2DD; 618036), Lassuthova et al. (2018) identified a heterozygous c.2432A-C … (more) In a 33-year-old Korean man (family 7) with autosomal dominant axonal Charcot-Marie-Tooth disease type 2DD (CMT2DD; 618036), Lassuthova et al. (2018) identified a heterozygous c.2432A-C transversion (c.2432A-C, NM_000701) in exon 19 of the ATP1A1 gene, resulting in an asp811-to-ala (D811A) substitution at a highly conserved residue in the fifth transmembrane domain where Na+ binding occurs. The mutation was found through the analysis of 513 whole exomes from 399 unrelated Korean families with CMT. The patient's unaffected mother did not carry the mutation, but DNA from the deceased father was unavailable; he reportedly had no symptoms of the disorder in his sixth decade. In vitro electrophysiologic functional expression studies in Xenopus oocytes showed that the mutation resulted in significantly fewer Na(+)-dependent currents compared to wildtype, consistent with a loss of function and haploinsufficiency. (less)
Uncertain significance (Oct 07, 2017)	no assertion criteria provided Method: literature only	Charcot-Marie-Tooth disease type 2A2 Affected status: yes Allele origin: germline	Inherited Neuropathy Consortium Ii, University Of Miami Accession: SCV004011910.1 First in ClinVar: Jul 16, 2023 Last updated: Jul 16, 2023	Publications: PubMed (1) PubMed: 8526465

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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mutations in ATP1A1 Cause Dominant Charcot-Marie-Tooth Type 2.	Lassuthova P	American journal of human genetics	2018	PMID: 29499166
Early copper therapy in classic Menkes disease patients with a novel splicing mutation.	Kaler SG	Annals of neurology	1995	PMID: 8526465

Text-mined citations for rs1553192783 ...

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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_000701.8(ATP1A1):c.2432A>C (p.Asp811Ala)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs1553192783 ...