ClinVar Miner

Submissions for variant NM_000143.4(FH):c.668_669del (p.Lys223fs)

dbSNP: rs886039364
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255892 SCV000321641 pathogenic not provided 2015-04-07 criteria provided, single submitter clinical testing The c.668_669delAA variant in the FH gene causes a frameshift starting with codon Lysine 223, changes this amino acid to a Arginine residue and creates a premature Stop codon at position 26 of the new reading frame, denoted p.Lys223ArgfsX26. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Although this variant has not been previously reported to our knowledge, we interpret it to be pathogenic.
Invitae RCV000255892 SCV001398443 pathogenic not provided 2023-12-19 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys223Argfs*26) in the FH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FH are known to be pathogenic (PMID: 11865300, 21398687). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FH-related conditions. ClinVar contains an entry for this variant (Variation ID: 265147). For these reasons, this variant has been classified as Pathogenic.
Myriad Genetics, Inc. RCV003456041 SCV004187897 pathogenic Hereditary leiomyomatosis and renal cell cancer 2023-07-05 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Baylor Genetics RCV003469195 SCV004197334 likely pathogenic Fumarase deficiency 2023-08-15 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000255892 SCV004225709 likely pathogenic not provided 2022-09-30 criteria provided, single submitter clinical testing PM2, PVS1

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