NM_001614.5(ACTG1):c.617G>A (p.Arg206Gln) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 26, 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:: RCV002295307.4

Allele description [Variation Report for NM_001614.5(ACTG1):c.617G>A (p.Arg206Gln)]

NM_001614.5(ACTG1):c.617G>A (p.Arg206Gln)

Gene:

ACTG1:actin gamma 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17q25.3

Genomic location:

Preferred name:

NM_001614.5(ACTG1):c.617G>A (p.Arg206Gln)

HGVS:

NC_000017.11:g.81511373C>T
NG_011433.1:g.6429G>A
NM_001199954.3:c.617G>A
NM_001614.5:c.617G>AMANE SELECT
NP_001186883.1:p.Arg206Gln
NP_001605.1:p.Arg206Gln
NC_000017.10:g.79478399C>T
NM_001199954.1:c.617G>A
NR_037688.3:n.689G>A

Protein change:

R206Q

Links:

dbSNP: rs1555666715

NCBI 1000 Genomes Browser:

rs1555666715

Molecular consequence:

NM_001199954.3:c.617G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001614.5:c.617G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_037688.3:n.689G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Autosomal dominant nonsyndromic hearing loss 20
Synonyms:: Deafness, autosomal dominant 20
Identifiers:: MONDO: MONDO:0011480; MedGen: C1858172; Orphanet: 90635; OMIM: 604717

Name:: Baraitser-winter syndrome 2
Identifiers:: MONDO: MONDO:0013812; MedGen: C3281235; Orphanet: 2995; OMIM: 614583

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002595508	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 26, 2022)	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

SCV002595508

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 26, 2022)

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	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002595508.3

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

Description

In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 not expected to disrupt ACTG1 protein function. ClinVar contains an entry for this variant (Variation ID: 517300). This missense change has been observed in individual(s) with deafness (Invitae). In at least one individual the variant was observed to be de novo. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 206 of the ACTG1 protein (p.Arg206Gln).

#	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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