ClinVar Miner

Submissions for variant NM_001159699.2(FHL1):c.506G>A (p.Cys169Tyr)

dbSNP: rs122458145
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003511981 SCV004298993 likely pathogenic X-linked myopathy with postural muscle atrophy 2023-07-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 153 of the FHL1 protein (p.Cys153Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with X-linked dominant FHL1-related conditions (PMID: 18274675, 26627873; Invitae). ClinVar contains an entry for this variant (Variation ID: 11553). 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. Experimental studies have shown that this missense change affects FHL1 function (PMID: 24634512). This variant disrupts the p.Cys153 amino acid residue in FHL1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18274675, 23965743). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000012309 SCV000032543 pathogenic Myopathy, reducing body, X-linked, childhood-onset 2008-03-01 no assertion criteria provided literature only

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