NM_178014.4(TUBB):c.43C>A (p.Gln15Lys) AND Multiple benign circumferential skin creases on limbs 1

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 1, 2013
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000203282.7

Allele description [Variation Report for NM_178014.4(TUBB):c.43C>A (p.Gln15Lys)]

NM_178014.4(TUBB):c.43C>A (p.Gln15Lys)

Gene:

TUBB:tubulin beta class I [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.33

Genomic location:

Preferred name:

NM_178014.4(TUBB):c.43C>A (p.Gln15Lys)

HGVS:

NC_000006.12:g.30720549C>A
NG_034142.1:g.5349C>A
NM_001293213.2:c.43C>A
NM_001293214.2:c.34+9C>A
NM_178014.4:c.43C>AMANE SELECT
NP_001280142.1:p.Gln15Lys
NP_821133.1:p.Gln15Lys
NC_000006.11:g.30688326C>A
NM_178014.3:c.43C>A
NR_120608.2:n.198C>A
P07437:p.Gln15Lys

Protein change:

Q15K; GLN15LYS

Links:

UniProtKB: P07437#VAR_076543; OMIM: 191130.0004; dbSNP: rs864321676

NCBI 1000 Genomes Browser:

rs864321676

Molecular consequence:

NM_001293214.2:c.34+9C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001293213.2:c.43C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_178014.4:c.43C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_120608.2:n.198C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Multiple benign circumferential skin creases on limbs 1
Synonyms:: Skin creases, multiple benign ring-shaped, of limbs; Kunze Riehm syndrome; CIRCUMFERENTIAL SKIN CREASES, KUNZE TYPE; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0020738; MedGen: C4551592; OMIM: 156610

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000258407	OMIM	no assertion criteria provided	Pathogenic (Apr 1, 2013)	germline	literature only	Leonard, N. J. A second patient with MCA/MR syndrome with multiple circumferential skin creases. Am. J. Med. Genet. 112: 91-94, 2002.

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000258407

OMIM

no assertion criteria provided

Pathogenic
(Apr 1, 2013)

germline

literature only

Leonard, N. J. A second patient with MCA/MR syndrome with multiple circumferential skin creases. Am. J. Med. Genet. 112: 91-94, 2002.

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Details of each submission

From OMIM, SCV000258407.5

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

Description

In a Canadian boy and a Turkish girl with congenital symmetric circumferential skin creases (CSCSC1; 156610), originally reported by Leonard (2002) and Ulucan et al. (2013), respectively, Isrie et al. (2015) identified heterozygosity for a c.43C-A transversion (c.43C-A, NM_178014.3) in the TUBB gene, resulting in a gln15-to-lys (Q15K) substitution. In both probands the mutation arose de novo. Kinetic analysis of TUBB heterodimer assembly reactions demonstrated a profound reduction in formation of the TBCD/beta-tubulin intermediate complex and an even greater reduction in the yield of assembled heterodimers with the Q15K mutant compared to wildtype. Microtubule plus-end tracking experiments showed a significant increase in velocity with overexpression of wildtype TUBB compared to control, but this increase was not seen with the Q15K mutant. (In the article by Isrie et al. (2015), the amino acid substitution is cited as gln15-to-lys in some places and as glu15-to-lys in others.)

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

Last Updated: Sep 23, 2023

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