NM_000424.4(KRT5):c.508G>A (p.Glu170Lys) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jun 7, 2023
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:: RCV000056603.13

Allele description [Variation Report for NM_000424.4(KRT5):c.508G>A (p.Glu170Lys)]

NM_000424.4(KRT5):c.508G>A (p.Glu170Lys)

Gene:

KRT5:keratin 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q13.13

Genomic location:

Preferred name:

NM_000424.4(KRT5):c.508G>A (p.Glu170Lys)

HGVS:

NC_000012.12:g.52519789C>T
NG_008297.1:g.5671G>A
NM_000424.4:c.508G>AMANE SELECT
NP_000415.2:p.Glu170Lys
NC_000012.11:g.52913573C>T
NM_000424.3:c.508G>A
P13647:p.Glu170Lys

Protein change:

E170K; GLU170LYS

Links:

UniProtKB: P13647#VAR_026537; OMIM: 148040.0020; dbSNP: rs59115483

NCBI 1000 Genomes Browser:

rs59115483

Molecular consequence:

NM_000424.4:c.508G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000087716	Epithelial Biology; Institute of Medical Biology, Singapore	no classification provided	not provided	not provided	not provided
SCV000321834	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jun 7, 2023)	germline	clinical testing	Citation Link,
SCV005198619	Clinical Genetics Laboratory, Skane University Hospital Lund	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 21, 2023)	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

SCV000087716

Epithelial Biology; Institute of Medical Biology, Singapore

no classification provided

not provided

SCV000321834

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jun 7, 2023)

germline

clinical testing

Citation Link,

SCV005198619

Clinical Genetics Laboratory, Skane University Hospital Lund

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 21, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

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

Details of each submission

From Epithelial Biology; Institute of Medical Biology, Singapore, SCV000087716.1

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

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

From GeneDx, SCV000321834.8

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

Description

Published functional studies demonstrate a damaging effect due to disruption of keratin intermediate filament alignment and formation, leading to cytoplasmic aggregates and a weakened cytoskeleton (Yasukawa et al., 2002); Located in the highly conserved helix initiation motif of the alpha-helical rod domain, which is intolerant to change; variants in this motif interfere with proper keratin intermediate filament assembly and function, resulting in skin fragility and/or hyperkeratosis (Chamcheu et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 20055872, 20030639, 31302245, 26432462, 17549391, 11990248, 21144712, 26707537, 28425111, 31589614, 12707098, 18704110, 16786515, 21176769, 11973334)

#	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 Clinical Genetics Laboratory, Skane University Hospital Lund, SCV005198619.1

#	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

Last Updated: Nov 24, 2024

ClinVar

Relating variation to medicine