NM_004859.4(CLTC):c.2669C>T (p.Pro890Leu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Dec 5, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001281635.8

Allele description [Variation Report for NM_004859.4(CLTC):c.2669C>T (p.Pro890Leu)]

NM_004859.4(CLTC):c.2669C>T (p.Pro890Leu)

Gene:

CLTC:clathrin heavy chain [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q23.1

Genomic location:

Preferred name:

NM_004859.4(CLTC):c.2669C>T (p.Pro890Leu)

HGVS:

NC_000017.11:g.59677061C>T
NG_047043.1:g.62373C>T
NM_001288653.2:c.2681C>T
NM_004859.4:c.2669C>TMANE SELECT
NP_001275582.1:p.Pro894Leu
NP_001275582.1:p.Pro894Leu
NP_004850.1:p.Pro890Leu
NC_000017.10:g.57754422C>T
NM_001288653.1:c.2681C>T
NM_004859.3:c.2669C>T
p.Pro894Leu

Protein change:

P890L; PRO890LEU

Links:

OMIM: 118955.0004

Molecular consequence:

NM_001288653.2:c.2681C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004859.4:c.2669C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001468971	Laboratoire de Génétique Moléculaire, CHU Bordeaux	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002526557	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 14, 2022)	germline	clinical testing	Citation Link,
SCV003297510	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 5, 2024)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29100083, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001468971

Laboratoire de Génétique Moléculaire, CHU Bordeaux

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic

germline

clinical testing

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

SCV002526557

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 14, 2022)

germline

clinical testing

Citation Link,

SCV003297510

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 5, 2024)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

High Rate of Recurrent De Novo Mutations in Developmental and Epileptic Encephalopathies.

Hamdan FF, Myers CT, Cossette P, Lemay P, Spiegelman D, Laporte AD, Nassif C, Diallo O, Monlong J, Cadieux-Dion M, Dobrzeniecka S, Meloche C, Retterer K, Cho MT, Rosenfeld JA, Bi W, Massicotte C, Miguet M, Brunga L, Regan BM, Mo K, Tam C, et al.

Am J Hum Genet. 2017 Nov 2;101(5):664-685. doi: 10.1016/j.ajhg.2017.09.008.

PubMed [citation]

PMID:: 29100083
PMCID:: PMC5673604

See all PubMed Citations (3)

Details of each submission

From Laboratoire de Génétique Moléculaire, CHU Bordeaux, SCV001468971.1

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

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

From GeneDx, SCV002526557.2

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

Description

Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Also known as P890L; This variant is associated with the following publications: (PMID: 28191890, 31036916, 31231135, 30979967, 26822784, 28135719, 30337205, 31776469, 31785789, 33004838, 29100083)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003297510.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 894 of the CLTC protein (p.Pro894Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with CLTC-related conditions (PMID: 29100083). In at least one individual the variant was observed to be de novo. This variant is also known as c.2669C>T (p.Pro890Leu). ClinVar contains an entry for this variant (Variation ID: 488418). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt CLTC protein function with a negative predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

#	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: Feb 25, 2025

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