NM_002968.3(SALL1):c.1214dup (p.Leu406fs) AND Townes syndrome

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 13, 2016
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:: RCV000548925.4

Allele description [Variation Report for NM_002968.3(SALL1):c.1214dup (p.Leu406fs)]

NM_002968.3(SALL1):c.1214dup (p.Leu406fs)

Gene:

SALL1:spalt like transcription factor 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

16q12.1

Genomic location:

Preferred name:

NM_002968.3(SALL1):c.1214dup (p.Leu406fs)

HGVS:

NC_000016.10:g.51141010dup
NG_007990.1:g.15265dup
NM_001127892.2:c.923dup
NM_002968.3:c.1214dupMANE SELECT
NP_001121364.1:p.Leu309fs
NP_002959.2:p.Leu406fs
LRG_674:g.15265dup
NC_000016.9:g.51174918_51174919insG
NC_000016.9:g.51174921dup
NM_002968.2:c.1214dupC

Protein change:

L309fs

Links:

dbSNP: rs1555475275

NCBI 1000 Genomes Browser:

rs1555475275

Molecular consequence:

NM_001127892.2:c.923dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002968.3:c.1214dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Townes syndrome (TBS)
Synonyms:: Townes-Brocks syndrome
Identifiers:: MONDO: MONDO:0007142; MeSH: C536974; MedGen: C0265246; Orphanet: 857; OMIM: PS107480

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000630904	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 13, 2016)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9973281, 16088922, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000630904

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 13, 2016)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Molecular analysis of SALL1 mutations in Townes-Brocks syndrome.

Kohlhase J, Taschner PE, Burfeind P, Pasche B, Newman B, Blanck C, Breuning MH, ten Kate LP, Maaswinkel-Mooy P, Mitulla B, Seidel J, Kirkpatrick SJ, Pauli RM, Wargowski DS, Devriendt K, Proesmans W, Gabrielli O, Coppa GV, Wesby-van Swaay E, Trembath RC, Schinzel AA, Reardon W, et al.

Am J Hum Genet. 1999 Feb;64(2):435-45.

PubMed [citation]

PMID:: 9973281
PMCID:: PMC1377753

SALL1 mutation analysis in Townes-Brocks syndrome: twelve novel mutations and expansion of the phenotype.

Botzenhart EM, Green A, Ilyina H, König R, Lowry RB, Lo IF, Shohat M, Burke L, McGaughran J, Chafai R, Pierquin G, Michaelis RC, Whiteford ML, Simola KO, Rösler B, Kohlhase J.

Hum Mutat. 2005 Sep;26(3):282.

PubMed [citation]

PMID:: 16088922

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000630904.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in SALL1 are known to be pathogenic (PMID: 9973281, 16088922). This sequence change inserts 1 nucleotide in exon 2 of the SALL1 mRNA (c.1214dupC), causing a frameshift at codon 406. This creates a premature translational stop signal (p.Leu406Phefs*32) and is expected to result in an absent or disrupted protein product.

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

Last Updated: Feb 28, 2024

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