ClinVar Miner

Submissions for variant NM_000143.4(FH):c.1209del (p.Phe403fs)

dbSNP: rs1060499644
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000445613 SCV000537263 pathogenic Hereditary leiomyomatosis and renal cell cancer 2017-01-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV001010289 SCV001170463 pathogenic Hereditary cancer-predisposing syndrome 2022-05-24 criteria provided, single submitter clinical testing The c.1209delT pathogenic mutation, located in coding exon 8 of the FH gene, results from a deletion of one nucleotide at nucleotide position 1209, causing a translational frameshift with a predicted alternate stop codon (p.F403Lfs*3). This alteration has been previously identified in the tumor and germline of one individual with renal cell carcinoma diagnosed between age 20-29y (Schrader KA et al. JAMA Oncol, 2016 Jan;2:104-11). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Labcorp Genetics (formerly Invitae), Labcorp RCV002525532 SCV002219601 pathogenic not provided 2020-11-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with renal cell cancer (PMID: 26556299). ClinVar contains an entry for this variant (Variation ID: 393580). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Phe403Leufs*3) 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).
Baylor Genetics RCV003463832 SCV004197386 likely pathogenic Fumarase deficiency 2022-08-12 criteria provided, single submitter clinical testing

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