NM_001614.5(ACTG1):c.773C>T (p.Pro258Leu) AND not provided

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Jan 26, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000991480.30

Allele description [Variation Report for NM_001614.5(ACTG1):c.773C>T (p.Pro258Leu)]

NM_001614.5(ACTG1):c.773C>T (p.Pro258Leu)

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.773C>T (p.Pro258Leu)

HGVS:

NC_000017.11:g.81511217G>A
NG_011433.1:g.6585C>T
NM_001199954.3:c.773C>T
NM_001614.5:c.773C>TMANE SELECT
NP_001186883.1:p.Pro258Leu
NP_001605.1:p.Pro258Leu
NC_000017.10:g.79478243G>A
NM_001614.3:c.773C>T
NR_037688.3:n.845C>T

Protein change:

P258L

Links:

dbSNP: rs11549191

NCBI 1000 Genomes Browser:

rs11549191

Molecular consequence:

NM_001199954.3:c.773C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001614.5:c.773C>T - missense variant - [Sequence Ontology: SO:0001583]
NR_037688.3:n.845C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001142905	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Pathogenic (Jan 21, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 28000701, 26467025
SCV001247664	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Apr 1, 2021)	germline	clinical testing	Citation Link,
SCV001782645	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jan 26, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001142905

Athena Diagnostics

criteria provided, single submitter

(Athena Diagnostics Criteria)

Pathogenic
(Jan 21, 2019)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV001247664

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Pathogenic
(Apr 1, 2021)

germline

clinical testing

Citation Link,

SCV001782645

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jan 26, 2022)

germline

clinical testing

Citation Link

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
not provided	germline	yes	2	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The diagnostic yield of whole-exome sequencing targeting a gene panel for hearing impairment in The Netherlands.

Zazo Seco C, Wesdorp M, Feenstra I, Pfundt R, Hehir-Kwa JY, Lelieveld SH, Castelein S, Gilissen C, de Wijs IJ, Admiraal RJ, Pennings RJ, Kunst HP, van de Kamp JM, Tamminga S, Houweling AC, Plomp AS, Maas SM, de Koning Gans PA, Kant SG, de Geus CM, Frints SG, Vanhoutte EK, et al.

Eur J Hum Genet. 2017 Feb;25(3):308-314. doi: 10.1038/ejhg.2016.182. Epub 2016 Dec 21.

PubMed [citation]

PMID:: 28000701
PMCID:: PMC5315517

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

Details of each submission

From Athena Diagnostics, SCV001142905.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Not found in the total gnomAD dataset, and the data is high quality (0/281966 chr). Predicted to have a damaging effect on the protein. One de novo case with parental identity confirmed.

#	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

From CeGaT Center for Human Genetics Tuebingen, SCV001247664.26

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	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		2	not provided	not provided	not provided

From GeneDx, SCV001782645.3

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

Description

Not observed in large population cohorts (gnomAD); Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28000701)

#	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

Last Updated: Oct 20, 2024

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