NM_006015.6(ARID1A):c.3524C>T (p.Pro1175Leu) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 25, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001582591.7

Allele description [Variation Report for NM_006015.6(ARID1A):c.3524C>T (p.Pro1175Leu)]

NM_006015.6(ARID1A):c.3524C>T (p.Pro1175Leu)

Genes:

ARID1A:AT-rich interaction domain 1A [Gene - OMIM - HGNC]
LOC126805670:CDK7 strongly-dependent group 2 enhancer GRCh37_chr1:27098665-27099864 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

1p36.11

Genomic location:

Preferred name:

NM_006015.6(ARID1A):c.3524C>T (p.Pro1175Leu)

HGVS:

NC_000001.11:g.26772617C>T
NG_029965.1:g.81587C>T
NM_006015.6:c.3524C>TMANE SELECT
NM_139135.4:c.3524C>T
NP_006006.3:p.Pro1175Leu
NP_624361.1:p.Pro1175Leu
LRG_875t1:c.3524C>T
LRG_875:g.81587C>T
NC_000001.10:g.27099108C>T
NM_006015.4:c.3524C>T

Protein change:

P1175L

Links:

dbSNP: rs145886877

NCBI 1000 Genomes Browser:

rs145886877

Molecular consequence:

NM_006015.6:c.3524C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_139135.4:c.3524C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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ABC transporter permease [Paraburkholderia acidiphila]
ABC transporter permease [Paraburkholderia acidiphila]
gi|1787160036|gnl|PRJNA534068|FAZ97 5|gb|QGZ54056.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001813281	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (May 26, 2020)	germline	clinical testing	Citation Link,
SCV003483573	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 25, 2024)	germline	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

SCV001813281

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely benign
(May 26, 2020)

germline

clinical testing

Citation Link,

SCV003483573

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 25, 2024)

germline

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	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001813281.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is associated with the following publications: (PMID: 24728327)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003483573.2

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1175 of the ARID1A protein (p.Pro1175Leu). This variant is present in population databases (rs145886877, gnomAD 0.009%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with ARID1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 133547). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ARID1A protein function with a positive predictive value of 80%. 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.

#	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

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