VCV003600416.1 - ClinVar

NM_001378687.1(ATP2C1):c.1818G>T (p.Gln606His)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance

This classification is based on the single submission received

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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001378687.1(ATP2C1):c.1818G>T (p.Gln606His)

Variation ID: 3600416 Accession: VCV003600416.1

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 3q22.1 3: 130980658 (GRCh38) [ NCBI UCSC ] 3: 130699502 (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	Feb 1, 2025	Feb 1, 2025	Jul 16, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001378687.1:c.1818G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001365616.1:p.Gln606His	missense
NM_001001485.3:c.1818G>T	NP_001001485.1:p.Gln606His	missense
NM_001001486.2:c.1818G>T	NP_001001486.1:p.Gln606His	missense
NM_001001487.2:c.1818G>T	NP_001001487.1:p.Gln606His	missense
NM_001199179.3:c.1818G>T	NP_001186108.1:p.Gln606His	missense
NM_001199180.2:c.1920G>T	NP_001186109.1:p.Gln640His	missense
NM_001199181.3:c.1920G>T	NP_001186110.1:p.Gln640His	missense
NM_001199182.2:c.1803G>T	NP_001186111.1:p.Gln601His	missense
NM_001199183.2:c.1770G>T	NP_001186112.1:p.Gln590His	missense
NM_001199184.3:c.1770G>T	NP_001186113.1:p.Gln590His	missense
NM_001199185.2:c.1818G>T	NP_001186114.1:p.Gln606His	missense
NM_001378511.1:c.1920G>T	NP_001365440.1:p.Gln640His	missense
NM_001378512.1:c.1818G>T	NP_001365441.1:p.Gln606His	missense
NM_001378513.1:c.1818G>T	NP_001365442.1:p.Gln606His	missense
NM_001378514.1:c.1770G>T	NP_001365443.1:p.Gln590His	missense
NM_014382.5:c.1818G>T	NP_055197.2:p.Gln606His	missense
NC_000003.12:g.130980658G>T
NC_000003.11:g.130699502G>T
NG_007379.2:g.135134G>T

... more HGVS ... less HGVS

Protein change

Q590H, Q601H, Q606H, Q640H

Other names

Canonical SPDI

NC_000003.12:130980657:G:T

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

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.
ATP2C1		-	-	GRCh38 GRCh37	302	348

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.
Familial benign pemphigus	Uncertain significance (1)	criteria provided, single submitter	Jul 16, 2024	RCV005052220.1

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.	Expand all rows Collapse all rows 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 (Jul 16, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Familial benign pemphigus	Clinical Genomics Laboratory, Washington University in St. Louis Accession: SCV005685271.1 First in ClinVar: Feb 01, 2025 Last updated: Feb 01, 2025	Comment: show An ATP2C1 c.1818G>T (p.Gln606His) variant was identified at a near heterozygous allelic fraction of 48.5%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature. This variant is observed on 21/1,613,082 alleles in the general population (gnomAD v.4.1.0). Another variant at thi position, ATP2C1 c.1816C>T (p.Gln606*), which results in a premature termination codon, has been reported in an individual with Hailey-Hailey disease (Dobson-Stone C et al., PMID: 11841554). Computational predictors are uncertain as to the impact of this variant on ATP2C1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the ATP2C1 c.1818G>T (p.Gln606His) variant is uncertain at this time. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

An ATP2C1 c.1818G>T (p.Gln606His) variant was identified at a near heterozygous allelic fraction of 48.5%, a frequency which may be consistent with germline origin. This variant, to our knowledge, has not been reported in the medical literature. This variant is observed on 21/1,613,082 alleles in the general population (gnomAD v.4.1.0). Another variant at thi position, ATP2C1 c.1816C>T (p.Gln606*), which results in a premature termination codon, has been reported in an individual with Hailey-Hailey disease (Dobson-Stone C et al., PMID: 11841554). Computational predictors are uncertain as to the impact of this variant on ATP2C1 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of the ATP2C1 c.1818G>T (p.Gln606His) variant is uncertain at this time.

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 this variant ...

Record last updated May 19, 2025

ClinVar Genomic variation as it relates to human health

NM_001378687.1(ATP2C1):c.1818G>T (p.Gln606His)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Citations for germline classification of this variant

Text-mined citations for this variant ...