VCV000206295.19 - ClinVar

NM_001184880.2(PCDH19):c.1294A>G (p.Met432Val)

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.

(8)

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.

Benign/Likely benign

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001184880.2(PCDH19):c.1294A>G (p.Met432Val)

Variation ID: 206295 Accession: VCV000206295.19

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xq22.1 X: 100407304 (GRCh38) [ NCBI UCSC ] X: 99662302 (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	Oct 8, 2024	Jan 22, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001184880.2:c.1294A>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001171809.1:p.Met432Val	missense
NM_001105243.2:c.1294A>G	NP_001098713.1:p.Met432Val	missense
NM_020766.3:c.1294A>G	NP_065817.2:p.Met432Val	missense
NC_000023.11:g.100407304T>C
NC_000023.10:g.99662302T>C
NG_021319.1:g.7970A>G
LRG_843:g.7970A>G
LRG_843t1:c.1294A>G	LRG_843p1:p.Met432Val

... more HGVS ... less HGVS

Protein change

M432V

Other names

p.M432V:ATG>GTG

Canonical SPDI

NC_000023.11:100407303:T: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.

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00039

Trans-Omics for Precision Medicine (TOPMed) 0.00047

The Genome Aggregation Database (gnomAD) 0.00071

Exome Aggregation Consortium (ExAC) 0.00073

The Genome Aggregation Database (gnomAD), exomes 0.00076

Links

ClinGen: CA316242 dbSNP: rs200728466 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.
PCDH19		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	1206	1514

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 specified	Benign (1)	criteria provided, single submitter	Jul 9, 2016	RCV000188330.10
Developmental and epileptic encephalopathy, 9	Likely benign (2)	criteria provided, single submitter	Jan 22, 2024	RCV000606264.9
not provided	Benign (3)	criteria provided, single submitter	Jun 14, 2019	RCV001706162.4
Inborn genetic diseases	Benign (1)	criteria provided, single submitter	May 22, 2019	RCV002381630.2
PCDH19-related disorder	Likely benign (1)	no assertion criteria provided	Jan 9, 2020	RCV003937663.2

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.
Benign (Jul 09, 2016)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000342998.4 First in ClinVar: Dec 06, 2016 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH19 Number of individuals with the variant: 1 Sex: mixed
Benign (Jun 14, 2019)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV000241942.10 First in ClinVar: Aug 07, 2015 Last updated: Mar 04, 2023	Comment: This variant is associated with the following publications: (PMID: 23334464)
Likely benign (Jan 22, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Developmental and epileptic encephalopathy, 9 Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001005456.5 First in ClinVar: Dec 17, 2019 Last updated: Feb 14, 2024
Benign (May 22, 2019)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Inborn genetic diseases Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV002692857.2 First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Likely benign (-)	no assertion criteria provided Method: clinical testing	Developmental and epileptic encephalopathy, 9 Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV000734798.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001928965.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001972649.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021
Likely benign (Jan 09, 2020)	no assertion criteria provided Method: clinical testing	PCDH19-related condition Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV004748935.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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

Title	Author	Journal	Year	Link
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PCDH19	-	-	-	-

Text-mined citations for rs200728466 ...

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 Oct 13, 2024

ClinVar Genomic variation as it relates to human health

NM_001184880.2(PCDH19):c.1294A>G (p.Met432Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs200728466 ...