ClinVar Miner

Submissions for variant NM_000143.4(FH):c.1391-1G>C

dbSNP: rs863223978
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000196540 SCV000251436 pathogenic not provided 2017-04-06 criteria provided, single submitter clinical testing The c.1391-1 G>C splice site mutation in the FH gene destroys the canonical splice acceptor site in intron 9. It is predicted to cause abnormal gene splicing. Although this mutation has not been previously reported to our knowledge, its presence is consistent with a diagnosis of hereditary leiomyomatosis and renal cell cancer. The variant is found in FH panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV000196540 SCV000937086 pathogenic not provided 2022-06-08 criteria provided, single submitter clinical testing Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 214387). Disruption of this splice site has been observed in individuals with clinical features of hereditary leiomyomatosis and renal cell cancer (PMID: 28266706, 28300276; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 9 of the FH gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product.
Baylor Genetics RCV004567400 SCV005057760 pathogenic Fumarase deficiency 2024-02-07 criteria provided, single submitter clinical testing

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