NM_001159699.2(FHL1):c.812G>A (p.Cys271Tyr) AND X-linked myopathy with postural muscle atrophy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 21, 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:: RCV000705293.9

Allele description [Variation Report for NM_001159699.2(FHL1):c.812G>A (p.Cys271Tyr)]

NM_001159699.2(FHL1):c.812G>A (p.Cys271Tyr)

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.812G>A (p.Cys271Tyr)

HGVS:

NC_000023.11:g.136209946G>A
NG_015895.1:g.67547G>A
NM_001159699.2:c.812G>AMANE SELECT
NM_001159700.2:c.764G>A
NM_001159701.2:c.851G>A
NM_001159702.3:c.964G>A
NM_001159703.2:c.577G>A
NM_001159704.1:c.764G>A
NM_001167819.1:c.764G>A
NM_001330659.2:c.625G>A
NM_001369326.1:c.964G>A
NM_001369327.2:c.964G>A
NM_001369328.1:c.964G>A
NM_001369329.1:c.764G>A
NM_001369330.1:c.764G>A
NM_001369331.1:c.764G>A
NM_001449.5:c.764G>A
NP_001153171.1:p.Cys271Tyr
NP_001153172.1:p.Cys255Tyr
NP_001153173.1:p.Cys284Tyr
NP_001153174.1:p.Ala322Thr
NP_001153175.1:p.Ala193Thr
NP_001153176.1:p.Cys255Tyr
NP_001161291.1:p.Cys255Tyr
NP_001317588.1:p.Ala209Thr
NP_001356255.1:p.Ala322Thr
NP_001356256.1:p.Ala322Thr
NP_001356257.1:p.Ala322Thr
NP_001356258.1:p.Cys255Tyr
NP_001356259.1:p.Cys255Tyr
NP_001356260.1:p.Cys255Tyr
NP_001440.2:p.Cys255Tyr
LRG_739t1:c.812G>A
LRG_739t2:c.964G>A
LRG_739:g.67547G>A
LRG_739p1:p.Cys271Tyr
LRG_739p2:p.Ala322Thr
NC_000023.10:g.135292105G>A
NM_001449.4:c.764G>A
NR_027621.2:n.1175G>A

Protein change:

A193T

Links:

dbSNP: rs869025431

NCBI 1000 Genomes Browser:

rs869025431

Molecular consequence:

NM_001159699.2:c.812G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159700.2:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159701.2:c.851G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159702.3:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159703.2:c.577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001159704.1:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001167819.1:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001330659.2:c.625G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369326.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369327.2:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369328.1:c.964G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369329.1:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369330.1:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001369331.1:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001449.5:c.764G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_027621.2:n.1175G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: X-linked myopathy with postural muscle atrophy
Identifiers:: MONDO: MONDO:0010401; MedGen: C2678055; OMIM: 300696

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000834283	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 21, 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

SCV000834283

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 21, 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, SCV000834283.5

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

Description

This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 255 of the FHL1 protein (p.Cys255Tyr). The cysteine residue is moderately conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant has not been reported in the literature in individuals with FHL1-related disease. 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. The p.Cys255Ser amino acid residue in FHL1 has been determined to be clinically significant (PMID:¬†25246303,¬†26857240). This suggests that variants that disrupt this residue are likely to be causative of disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0").

#	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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