NM_001318895.3(FHL2):c.568G>A (p.Ala190Thr) AND Primary dilated cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 31, 2020
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:: RCV001365220.4

Allele description [Variation Report for NM_001318895.3(FHL2):c.568G>A (p.Ala190Thr)]

NM_001318895.3(FHL2):c.568G>A (p.Ala190Thr)

Genes:

C2orf49:chromosome 2 open reading frame 49 [Gene - HGNC]
FHL2:four and a half LIM domains 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q12.2

Genomic location:

Preferred name:

NM_001318895.3(FHL2):c.568G>A (p.Ala190Thr)

HGVS:

NC_000002.12:g.105363405C>T
NG_008844.2:g.80369G>A
NM_001039492.3:c.568G>A
NM_001318894.1:c.568G>A
NM_001318895.3:c.568G>AMANE SELECT
NM_001318896.2:c.568G>A
NM_001318897.2:c.226G>A
NM_001318898.2:c.226G>A
NM_001318899.2:c.244G>A
NM_001374399.1:c.568G>A
NM_001450.4:c.568G>A
NM_201555.3:c.568G>A
NM_201557.5:c.568G>A
NP_001034581.1:p.Ala190Thr
NP_001305823.1:p.Ala190Thr
NP_001305824.1:p.Ala190Thr
NP_001305825.1:p.Ala190Thr
NP_001305826.1:p.Ala76Thr
NP_001305827.1:p.Ala76Thr
NP_001305828.1:p.Ala82Thr
NP_001361328.1:p.Ala190Thr
NP_001441.4:p.Ala190Thr
NP_963849.1:p.Ala190Thr
NP_963851.2:p.Ala190Thr
LRG_740t1:c.568G>A
LRG_740t2:c.568G>A
LRG_740t3:c.568G>A
LRG_740:g.80369G>A
LRG_740p1:p.Ala190Thr
LRG_740p2:p.Ala190Thr
LRG_740p3:p.Ala190Thr
NC_000002.11:g.105979862C>T

Protein change:

A190T

Links:

dbSNP: rs1279971079

NCBI 1000 Genomes Browser:

rs1279971079

Molecular consequence:

NM_001039492.3:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318894.1:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318895.3:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318896.2:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318897.2:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318898.2:c.226G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001318899.2:c.244G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001374399.1:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001450.4:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201555.3:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_201557.5:c.568G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001561483	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 31, 2020)	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

SCV001561483

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 31, 2020)

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, SCV001561483.3

#	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 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with FHL2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with threonine at codon 190 of the FHL2 protein (p.Ala190Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine.

#	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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