NM_005631.5(SMO):c.1234C>T (p.Leu412Phe) AND Curry-Jones syndrome

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 22, 2019
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:: RCV000236033.7

Allele description [Variation Report for NM_005631.5(SMO):c.1234C>T (p.Leu412Phe)]

NM_005631.5(SMO):c.1234C>T (p.Leu412Phe)

Gene:

SMO:smoothened, frizzled class receptor [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7q32.1

Genomic location:

Preferred name:

NM_005631.5(SMO):c.1234C>T (p.Leu412Phe)

HGVS:

NC_000007.14:g.129206557C>T
NG_023340.2:g.22686C>T
NM_005631.5:c.1234C>TMANE SELECT
NP_005622.1:p.Leu412Phe
LRG_1393t1:c.1234C>T
LRG_1393:g.22686C>T
LRG_1393p1:p.Leu412Phe
NC_000007.13:g.128846398C>T
NG_023340.1:g.22686C>T
NM_005631.4:c.1234C>T
Q99835:p.Leu412Phe

Protein change:

L412F; LEU412PHE

Links:

UniProtKB: Q99835#VAR_077087; OMIM: 601500.0003; dbSNP: rs879255280

NCBI 1000 Genomes Browser:

rs879255280

Molecular consequence:

NM_005631.5:c.1234C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Curry-Jones syndrome (CRJS)
Synonyms:: Craniofacial malformations, asymmetric, with polysyndactyly and abnormal skin and gut development
Identifiers:: MONDO: MONDO:0011134; MedGen: C0795915; Orphanet: 1553; OMIM: 601707

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000292563	OMIM	no assertion criteria provided	Pathogenic (Oct 11, 2019)	somatic	literature only	PubMed (5) [See all records that cite these PMIDs] 3144990, 7606318, 16531740, 18798318, 27236920
SCV000930574	Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 22, 2019)	somatic	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

SCV000292563

OMIM

no assertion criteria provided

Pathogenic
(Oct 11, 2019)

somatic

literature only

PubMed (5)
[See all records that cite these PMIDs]

SCV000930574

Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 22, 2019)

somatic

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

Citations

PubMed

Craniosynostosis update 1987.

Cohen MM Jr.

Am J Med Genet Suppl. 1988;4:99-148. Review.

PubMed [citation]

PMID:: 3144990

Craniofacial abnormalities, agenesis of the corpus callosum, polysyndactyly and abnormal skin and gut development--the Curry Jones syndrome.

Temple IK, Eccles DM, Winter RM, Baraitser M, Carr SB, Shortland D, Jones MC, Curry C.

Clin Dysmorphol. 1995 Apr;4(2):116-29.

PubMed [citation]

PMID:: 7606318

See all PubMed Citations (6)

Details of each submission

From OMIM, SCV000292563.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (5)

Description

In 8 patients with Curry-Jones syndrome (CRJS; 601707), including the 2 patients originally reported by Curry and Jones (Cohen, 1988) and 4 other patients previously reported by Temple et al. (1995), Thomas et al. (2006), and Grange et al. (2008), Twigg et al. (2016) identified somatic mosaicism in affected tissue samples for a c.1234C-T transition (c.1234C-T, NM_005631.4) in the SMOH gene, resulting in a leu412-to-phe (L412F) substitution in the transmembrane helix 5 within a pivot region. The mutant allele was present at levels substantially below 50% in the samples. Given the widespread mosaicism in these patients, the authors suggested that the mutation arises postzygotically early during embryonic development. Twigg et al. (2016) noted that the L412F mutation had previously been identified in ameloblastoma, medulloblastoma, meningioma, and basal cell carcinoma, and had been reported as the oncogenic driver in some of those tumors.

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

From Undiagnosed Diseases Network, NIH - Undiagnosed Diseases Network (NIH), UDN, SCV000930574.1

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

Description

A somatic c.1234C>T (p.L412F) pathogenic variant in the SMO gene was detected in this individualâ€™s affected skin sample. Whole genome sequencing analysis of this region on this individualâ€™s unaffected skin sample and parental samples for this individual did not detect the c.1234C>T (p.L412F) change, suggesting it arose in this individualâ€™s somatic tissues as a mosaic change. The c.1234C>T (p.L412F) variant has been reported as a recurrent somatic mutation in multiple affected individuals [PMID 27236920].

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

Last Updated: Jun 23, 2024

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