NM_001184880.2(PCDH19):c.1696C>G (p.Pro566Ala) AND Developmental and epileptic encephalopathy, 9

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 18, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001897441.4

Allele description [Variation Report for NM_001184880.2(PCDH19):c.1696C>G (p.Pro566Ala)]

NM_001184880.2(PCDH19):c.1696C>G (p.Pro566Ala)

Gene:

PCDH19:protocadherin 19 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq22.1

Genomic location:

Preferred name:

NM_001184880.2(PCDH19):c.1696C>G (p.Pro566Ala)

HGVS:

NC_000023.11:g.100406902G>C
NG_021319.1:g.8372C>G
NM_001105243.2:c.1696C>G
NM_001184880.2:c.1696C>GMANE SELECT
NM_020766.3:c.1696C>G
NP_001098713.1:p.Pro566Ala
NP_001171809.1:p.Pro566Ala
NP_065817.2:p.Pro566Ala
LRG_843t1:c.1696C>G
LRG_843:g.8372C>G
LRG_843p1:p.Pro566Ala
NC_000023.10:g.99661900G>C

Protein change:

P566A

Links:

dbSNP: rs1928370474

NCBI 1000 Genomes Browser:

rs1928370474

Molecular consequence:

NM_001105243.2:c.1696C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001184880.2:c.1696C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_020766.3:c.1696C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 9 (DEE9)
Synonyms:: EPILEPSY, FEMALE-RESTRICTED, WITH MENTAL RETARDATION; JUBERG-HELLMAN SYNDROME; PCDH19-Related X-Linked Female-Limited Epilepsy with Mental Retardation; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010246; MedGen: C1848137; Orphanet: 2076; OMIM: 300088

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Homo sapiens zinc finger protein 672, mRNA (cDNA clone IMAGE:5175166)
Homo sapiens zinc finger protein 672, mRNA (cDNA clone IMAGE:5175166)
gi|20381058|gb|BC029310.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002149188	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 18, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002149188

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 18, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002149188.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PCDH19 protein function. This variant has not been reported in the literature in individuals affected with PCDH19-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces proline with alanine at codon 566 of the PCDH19 protein (p.Pro566Ala). The proline residue is highly conserved and there is a small physicochemical difference between proline and alanine.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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