NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn) AND not specified

Germline classification:: Benign (6 submissions)
Last evaluated:: Apr 29, 2021
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:: RCV000296313.18

Allele description [Variation Report for NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)]

NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)

Gene:

FHL1:four and a half LIM domains 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

Xq26.3

Genomic location:

Preferred name:

NM_001159699.2(FHL1):c.871G>A (p.Asp291Asn)

HGVS:

NC_000023.11:g.136210005G>A
NG_015895.1:g.67606G>A
NM_001159699.2:c.871G>AMANE SELECT
NM_001159700.2:c.823G>A
NM_001159701.2:c.910G>A
NM_001159702.3:c.*51G>A
NM_001159703.2:c.*51G>A
NM_001159704.1:c.823G>A
NM_001167819.1:c.823G>A
NM_001330659.2:c.*51G>A
NM_001369326.1:c.*51G>A
NM_001369327.2:c.*51G>A
NM_001369328.1:c.*51G>A
NM_001369329.1:c.823G>A
NM_001369330.1:c.823G>A
NM_001369331.1:c.823G>A
NM_001449.5:c.823G>A
NP_001153171.1:p.Asp291Asn
NP_001153172.1:p.Asp275Asn
NP_001153173.1:p.Asp304Asn
NP_001153176.1:p.Asp275Asn
NP_001161291.1:p.Asp275Asn
NP_001356258.1:p.Asp275Asn
NP_001356259.1:p.Asp275Asn
NP_001356260.1:p.Asp275Asn
NP_001440.2:p.Asp275Asn
LRG_739t1:c.871G>A
LRG_739t2:c.*51G>A
LRG_739:g.67606G>A
LRG_739p1:p.Asp291Asn
NC_000023.10:g.135292164G>A
NM_001159702.2:c.*51G>A
NM_001449.4:c.823G>A
NR_027621.2:n.1234G>A

Protein change:

D275N

Links:

dbSNP: rs151315725

NCBI 1000 Genomes Browser:

rs151315725

Molecular consequence:

NM_001159702.3:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001159703.2:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001330659.2:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369326.1:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369327.2:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001369328.1:c.*51G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001159699.2:c.871G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159700.2:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159701.2:c.910G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159704.1:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167819.1:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369329.1:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369330.1:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369331.1:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001449.5:c.823G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027621.2:n.1234G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000336163	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Dec 3, 2015)	germline	clinical testing	Citation Link,
SCV000522548	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Mar 4, 2016)	germline	clinical testing	Citation Link,
SCV001623250	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Benign (Apr 29, 2021)	germline	clinical testing	Citation Link,
SCV001921766	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001930630	Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001965230	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Eurofins Ntd Llc (ga), SCV000336163.4

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

From GeneDx, SCV000522548.4

#	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 considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001623250.1

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

Description

Variant summary: FHL1 c.*51G>A is located in the untranslated mRNA region downstream of the termination codon. The variant allele was found at a frequency of 0.011 in 183528 control chromosomes in the gnomAD database, including 17 homozygotes. The observed variant frequency is approximately 28 fold of the estimated maximal expected allele frequency for a pathogenic variant in FHL1 causing Emery-Dreifuss Muscular Dystrophy phenotype (0.00039), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.*51G>A in individuals affected with Emery-Dreifuss Muscular Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001921766.1

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

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV001930630.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001965230.1

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

Last Updated: Oct 13, 2024

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