ClinVar Miner

Submissions for variant NM_000143.3(FH):c.892G>C (p.Ala298Pro) (rs201395553)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000442479 SCV000231479 uncertain significance not provided 2015-05-28 criteria provided, single submitter clinical testing
GeneDx RCV000442479 SCV000520991 likely pathogenic not provided 2018-07-10 criteria provided, single submitter clinical testing The A298P variant has been reported previously in association with uterine fibroids and decreased fumarate hydratase activity (Kubinova et al., 2013). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A298P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties; however, this substitution occurs at a position that is not conserved. A missense variant in a nearby residue (L303S) has been reported in the Human Gene Mutation Database in association with fumarase deficiency (Stenson et al., 2014), supporting the functional importance of this region of the protein. Based on the currently available information, we consider this variant to be likely pathogenic; however, the possibility that it is benign cannot be excluded.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000445630 SCV000537247 uncertain significance Multiple cutaneous leiomyomas 2017-01-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV000493248 SCV000581630 likely pathogenic Hereditary cancer-predisposing syndrome 2018-06-13 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Deficient protein function in appropriate functional assay(s);Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation;Rarity in general population databases (dbsnp, esp, 1000 genomes)

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