NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 20, 2023
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:: RCV003556110.1

Allele description

NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln)

Gene:

ACTN1:actinin alpha 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q24.1

Genomic location:

Preferred name:

NM_001130004.2(ACTN1):c.2255G>A (p.Arg752Gln)

HGVS:

NC_000014.9:g.68879987C>T
NG_029480.1:g.104380G>A
NM_001102.4:c.2255G>A
NM_001130004.1:c.2255G>A
NM_001130004.2:c.2255G>AMANE SELECT
NM_001130005.2:c.2255G>A
NP_001093.1:p.Arg752Gln
NP_001123476.1:p.Arg752Gln
NP_001123477.1:p.Arg752Gln
LRG_886t1:c.2255G>A
LRG_886:g.104380G>A
NC_000014.8:g.69346704C>T
NM_001102.3:c.2255G>A
P12814:p.Arg752Gln

Protein change:

R752Q; ARG752GLN

Links:

UniProtKB: P12814#VAR_069916; OMIM: 102575.0003; dbSNP: rs387907347

NCBI 1000 Genomes Browser:

rs387907347

Molecular consequence:

NM_001102.4:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130004.2:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001130005.2:c.2255G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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PREDICTED: Homo sapiens LIM homeobox 1 (LHX1), transcript variant X1, mRNA
PREDICTED: Homo sapiens LIM homeobox 1 (LHX1), transcript variant X1, mRNA
gi|2462491197|ref|XM_054329298.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004297113	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 20, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 31365757, 23434115, 25361813, 30351444, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004297113

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 20, 2023)

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

Investigation of calmodulin-like and rod domain mutations suggests common molecular mechanism for α-actinin-1-linked congenital macrothrombocytopenia.

O'Sullivan LR, Ajaykumar AP, Dembicka KM, Murphy A, Grennan EP, Young PW.

FEBS Lett. 2020 Jan;594(1):161-174. doi: 10.1002/1873-3468.13562. Epub 2019 Aug 9.

PubMed [citation]

PMID:: 31365757

ACTN1 mutations cause congenital macrothrombocytopenia.

Kunishima S, Okuno Y, Yoshida K, Shiraishi Y, Sanada M, Muramatsu H, Chiba K, Tanaka H, Miyazaki K, Sakai M, Ohtake M, Kobayashi R, Iguchi A, Niimi G, Otsu M, Takahashi Y, Miyano S, Saito H, Kojima S, Ogawa S.

Am J Hum Genet. 2013 Mar 7;92(3):431-8. doi: 10.1016/j.ajhg.2013.01.015. Epub 2013 Feb 21.

PubMed [citation]

PMID:: 23434115
PMCID:: PMC3591851

See all PubMed Citations (5)

Details of each submission

From Invitae, SCV004297113.1

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

Description

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. Experimental studies have shown that this missense change affects ACTN1 function (PMID: 23434115, 31365757). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 42030). This missense change has been observed in individual(s) with ACTN1-related conditions (PMID: 23434115, 25361813, 30351444). This variant is present in population databases (rs387907347, gnomAD 0.006%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 752 of the ACTN1 protein (p.Arg752Gln).

#	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: May 7, 2024

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