NM_014141.6(CNTNAP2):c.1123C>T (p.Pro375Ser) AND Cortical dysplasia-focal epilepsy syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 22, 2022
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:: RCV001039684.5

Allele description [Variation Report for NM_014141.6(CNTNAP2):c.1123C>T (p.Pro375Ser)]

NM_014141.6(CNTNAP2):c.1123C>T (p.Pro375Ser)

Gene:

CNTNAP2:contactin associated protein 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q35

Genomic location:

Preferred name:

NM_014141.6(CNTNAP2):c.1123C>T (p.Pro375Ser)

HGVS:

NC_000007.14:g.147132284C>T
NG_007092.3:g.1021284C>T
NM_014141.6:c.1123C>TMANE SELECT
NP_054860.1:p.Pro375Ser
NC_000007.13:g.146829376C>T
NG_007092.2:g.1020924C>T
NM_014141.5:c.1123C>T

Protein change:

P375S

Links:

dbSNP: rs757993314

NCBI 1000 Genomes Browser:

rs757993314

Molecular consequence:

NM_014141.6:c.1123C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cortical dysplasia-focal epilepsy syndrome (PTHSL1)
Synonyms:: Pitt-Hopkins-like syndrome 1
Identifiers:: MONDO: MONDO:0012400; MedGen: C2750246; Orphanet: 221150; OMIM: 610042

Recent activity

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transcription activator BRG1 [Trichuris trichiura]
transcription activator BRG1 [Trichuris trichiura]
gi|669226377|emb|CDW52317.1|

Protein
C405765 (1)
MeSH
N-myristoyl-alaninol [Supplementary Concept]
N-myristoyl-alaninol [Supplementary Concept]
structure in first source<br/>Date introduced: March 29, 2000<br/>

MeSH
U3 small nucleolar RNA-associated protein 4 homolog [Mus musculus]
U3 small nucleolar RNA-associated protein 4 homolog [Mus musculus]
gi|163954951|ref|NP_035704.2|

Protein
Mus musculus solute carrier family 16 (monocarboxylic acid transporters), member...
Mus musculus solute carrier family 16 (monocarboxylic acid transporters), member 7, mRNA (cDNA clone MGC:143699 IMAGE:40092297), complete cds
gi|109734468|gb|BC117803.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001203225	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 22, 2022)	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

SCV001203225

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 22, 2022)

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, SCV001203225.4

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

Description

This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 375 of the CNTNAP2 protein (p.Pro375Ser). This variant is present in population databases (rs757993314, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. ClinVar contains an entry for this variant (Variation ID: 453068). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.

#	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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