Submissions for variant NM_001159699.2(FHL1):c.534C>G (p.Cys178Trp)

dbSNP: rs377693754

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000292612	SCV000339927	uncertain significance	not provided	2016-03-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000537056	SCV000647047	uncertain significance	X-linked myopathy with postural muscle atrophy	2024-07-23	criteria provided, single submitter	clinical testing	This sequence change replaces cysteine, which is neutral and slightly polar, with tryptophan, which is neutral and slightly polar, at codon 162 of the FHL1 protein (p.Cys162Trp). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FHL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 286484). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
GeneDx	RCV000292612	SCV001992340	uncertain significance	not provided	2022-06-22	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Illumina Laboratory Services, Illumina	RCV004547710	SCV002034758	uncertain significance	FHL1-related disorder	2021-07-29	criteria provided, single submitter	clinical testing	The FHL1 c.486C>G (p.Cys162Trp) variant is a missense variant. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. This variant is not found in version 2.1.1 or version 3.1.1 of the Genome Aggregation Database despite its location in a region of good sequencing coverage, which suggest that the variant is rare. The p.Cys162Trp variant lies within the LIM zinc-binding 3 domain of the protein and affects one of the conserved cysteine residues critical for binding zinc ions (Wei et al. 2020). Based on the available evidence, the p.Cys162Trp variant is classified as a variant of uncertain significance for FHL1-related disorders.
Ambry Genetics	RCV002338847	SCV002634931	uncertain significance	Cardiovascular phenotype	2022-07-11	criteria provided, single submitter	clinical testing	The p.C162W variant (also known as c.486C>G), located in coding exon 3 of the FHL1 gene, results from a C to G substitution at nucleotide position 486. The cysteine at codon 162 is replaced by tryptophan, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000292612	SCV003832593	uncertain significance	not provided	2022-11-21	criteria provided, single submitter	clinical testing