NM_003900.5(SQSTM1):c.1060_1061del (p.Gln354fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 19, 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:: RCV002570530.3

Allele description [Variation Report for NM_003900.5(SQSTM1):c.1060_1061del (p.Gln354fs)]

NM_003900.5(SQSTM1):c.1060_1061del (p.Gln354fs)

Gene:

SQSTM1:sequestosome 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

5q35.3

Genomic location:

Preferred name:

NM_003900.5(SQSTM1):c.1060_1061del (p.Gln354fs)

HGVS:

NC_000005.10:g.179833677_179833678del
NG_011342.1:g.32290_32291del
NM_001142298.2:c.808_809del
NM_001142299.2:c.808_809del
NM_003900.5:c.1060_1061delMANE SELECT
NP_001135770.1:p.Gln270fs
NP_001135771.1:p.Gln270fs
NP_003891.1:p.Gln354fs
NC_000005.9:g.179260677_179260678del
NC_000005.9:g.179260677_179260678del
NM_001142298.1:c.808_809del

Protein change:

Q270fs

Links:

dbSNP: rs781417955

NCBI 1000 Genomes Browser:

rs781417955

Molecular consequence:

NM_001142298.2:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001142299.2:c.808_809del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003900.5:c.1060_1061del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Frontotemporal dementia and/or amyotrophic lateral sclerosis 1 (FTDALS1)
Synonyms:: Frontotemporal dementia with motor neuron disease 1
Identifiers:: MONDO: MONDO:0007105; MedGen: C5779877; Orphanet: 275872; OMIM: 105550

Name:: Paget disease of bone 2, early-onset (PDB2)
Synonyms:: Paget disease of bone 2
Identifiers:: MONDO: MONDO:0011183; MedGen: C4085251; OMIM: 602080

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003282862	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 19, 2022)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15146436, 21073987, 22491873, 23117207, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003282862

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 19, 2022)

germline

clinical testing

PubMed (5)
[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

Familial Paget's disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations.

Eekhoff EW, Karperien M, Houtsma D, Zwinderman AH, Dragoiescu C, Kneppers AL, Papapoulos SE.

Arthritis Rheum. 2004 May;50(5):1650-4. Erratum in: Arthritis Rheum. 2004 Jun;50(6):2040.

PubMed [citation]

PMID:: 15146436

Novel SQSTM1 mutations in patients with Paget's disease of bone in an unrelated multiethnic American population.

Michou L, Morissette J, Gagnon ER, Marquis A, Dellabadia M, Brown JP, Siris ES.

Bone. 2011 Mar 1;48(3):456-60. doi: 10.1016/j.bone.2010.11.004. Epub 2010 Nov 10.

PubMed [citation]

PMID:: 21073987

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003282862.2

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

Description

ClinVar contains an entry for this variant (Variation ID: 976109). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant disrupts the region of the SQSTM1 protein between codon 349 and 404. Other variants in this region have been observed in individuals with autosomal dominant SQSTM1-related conditions (PMID: 15146436, 21073987, 22491873, 23117207), which suggests that this may be a clinically significant region of the protein. This variant has not been reported in the literature in individuals affected with SQSTM1-related conditions. This variant is present in population databases (rs781417955, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Gln354Valfs*37) in the SQSTM1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 87 amino acid(s) of the SQSTM1 protein.

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine