NM_004924.6(ACTN4):c.763A>G (p.Lys255Glu) AND Focal segmental glomerulosclerosis 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 19, 2021
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:: RCV000005753.4

Allele description [Variation Report for NM_004924.6(ACTN4):c.763A>G (p.Lys255Glu)]

NM_004924.6(ACTN4):c.763A>G (p.Lys255Glu)

Gene:

ACTN4:actinin alpha 4 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

19q13.2

Genomic location:

Preferred name:

NM_004924.6(ACTN4):c.763A>G (p.Lys255Glu)

Other names:

K228E

HGVS:

NC_000019.10:g.38710286A>G
NG_007082.2:g.67600A>G
NM_001322033.2:c.733+810A>G
NM_004924.6:c.763A>GMANE SELECT
NP_004915.2:p.Lys255Glu
NC_000019.9:g.39200926A>G
O43707:p.Lys255Glu

Protein change:

K255E; LYS228GLU

Links:

UniProtKB: O43707#VAR_010378; OMIM: 604638.0001; dbSNP: rs121908415

NCBI 1000 Genomes Browser:

rs121908415

Molecular consequence:

NM_001322033.2:c.733+810A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_004924.6:c.763A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Focal segmental glomerulosclerosis 1 (FSGS1)
Identifiers:: MONDO: MONDO:0011303; MedGen: C4551527; Orphanet: 656; OMIM: 603278

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000025935	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 2000)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV002810533	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 19, 2021)	unknown	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

SCV000025935

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 2000)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV002810533

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 19, 2021)

unknown

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	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in ACTN4, encoding alpha-actinin-4, cause familial focal segmental glomerulosclerosis.

Kaplan JM, Kim SH, North KN, Rennke H, Correia LA, Tong HQ, Mathis BJ, Rodríguez-Pérez JC, Allen PG, Beggs AH, Pollak MR.

Nat Genet. 2000 Mar;24(3):251-6.

PubMed [citation]

PMID:: 10700177

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000025935.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In affected individuals in a family with focal segmental glomerulosclerosis that mapped to 19q (FSGS1; 603278), Kaplan et al. (2000) found a lys228-to-gly (K228G) mutation caused by a 682A-G nucleotide substitution in the ACTN4 RNA. The disease in this family, like that in 2 others studied, showed a mild increase in urine protein excretion starting in the teenage years or later, slowly progressive renal dysfunction, and the development of end-stage renal failure in some affected individuals. Two individuals in this family carrying the lys228-to-glu allele had no clinical symptoms.

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

From Fulgent Genetics, Fulgent Genetics, SCV002810533.1

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

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

Last Updated: Feb 20, 2024

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