NM_024577.4(SH3TC2):c.3341del (p.Pro1114fs) AND Charcot-Marie-Tooth disease type 4C

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 22, 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:: RCV000020897.4

Allele description [Variation Report for NM_024577.4(SH3TC2):c.3341del (p.Pro1114fs)]

NM_024577.4(SH3TC2):c.3341del (p.Pro1114fs)

Gene:

SH3TC2:SH3 domain and tetratricopeptide repeats 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q32

Genomic location:

Preferred name:

NM_024577.4(SH3TC2):c.3341del (p.Pro1114fs)

HGVS:

NC_000005.10:g.149008989del
NG_007947.2:g.59187del
NM_024577.4:c.3341delMANE SELECT
NP_078853.2:p.Pro1114fs
LRG_269:g.59187del
NC_000005.9:g.148388552del
NM_024577.3:c.3341delC

Protein change:

P1114fs

Links:

dbSNP: rs80338936

NCBI 1000 Genomes Browser:

rs80338936

Molecular consequence:

NM_024577.4:c.3341del - frameshift variant - [Sequence Ontology: SO:0001589]

Observations:

Condition(s)

Name:: Charcot-Marie-Tooth disease type 4C (CMT4C)
Synonyms:: CHARCOT-MARIE-TOOTH DISEASE, DEMYELINATING, AUTOSOMAL RECESSIVE, TYPE 4C; CMT 4C; Charcot-Marie-Tooth Neuropathy Type 4C (CMT4C); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011113; MedGen: C1866636; Orphanet: 99949; OMIM: 601596

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000041496	GeneReviews	no classification provided	not provided	unknown	literature only	PubMed (2) [See all records that cite these PMIDs] 14574644, 20301514
SCV002521525	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 14574644, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000041496

GeneReviews

no classification provided

not provided

unknown

literature only

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

SCV002521525

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 22, 2022)

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	1	not provided	not provided	1	not provided	clinical testing
not provided	unknown	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Azzedine H, Salih MA.

2008 Mar 31 [updated 2021 Mar 11]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A, editors. GeneReviews(®) [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2025.

PubMed [citation]

PMID:: 20301514

Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy.

Senderek J, Bergmann C, Stendel C, Kirfel J, Verpoorten N, De Jonghe P, Timmerman V, Chrast R, Verheijen MH, Lemke G, Battaloglu E, Parman Y, Erdem S, Tan E, Topaloglu H, Hahn A, Müller-Felber W, Rizzuto N, Fabrizi GM, Stuhrmann M, Rudnik-Schöneborn S, Züchner S, et al.

Am J Hum Genet. 2003 Nov;73(5):1106-19. Epub 2003 Oct 21.

PubMed [citation]

PMID:: 14574644
PMCID:: PMC1180490

See all PubMed Citations (3)

Details of each submission

From GeneReviews, SCV000041496.2

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

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

From 3billion, SCV002521525.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported to be associated with SH3TC2 related disorder (ClinVar ID: VCV000021699 / PMID: 14574644). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.

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

Last Updated: Sep 16, 2024

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