NM_000424.4(KRT5):c.1408T>C (p.Tyr470His) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV002461691.1

Allele description [Variation Report for NM_000424.4(KRT5):c.1408T>C (p.Tyr470His)]

NM_000424.4(KRT5):c.1408T>C (p.Tyr470His)

Genes:

LOC126861525:BRD4-independent group 4 enhancer GRCh37_chr12:52909857-52911056 [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.1408T>C (p.Tyr470His)

HGVS:

NC_000012.12:g.52516668A>G
NG_008297.1:g.8792T>C
NG_086024.1:g.696A>G
NM_000424.4:c.1408T>CMANE SELECT
NP_000415.2:p.Tyr470His
NC_000012.11:g.52910452A>G
NM_000424.3:c.1408T>C

Protein change:

Y470H

Molecular consequence:

NM_000424.4:c.1408T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: CN517202

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002756621	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Nov 15, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002756621

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Nov 15, 2022)

germline

clinical testing

Citation Link

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

Details of each submission

From GeneDx, SCV002756621.1

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

Description

Located in the 2B domain adjacent to the helix termination motif, which is highly conserved across all species and among all members of the keratin family; keratin gene variants affecting the residues at the ends of the central rod domains of the keratin proteins (helix initiation and termination motifs) interfere with proper keratin intermediate filament assembly and function, resulting in skin fragility, blistering, and/or hyperkeratosis (Chamcheu et al., 2011); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 23993914, 21176769)

#	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: Mar 26, 2023

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