ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.620A>T (p.His207Leu)

gnomAD frequency: 0.00002  dbSNP: rs202038890
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000469377 SCV000549947 uncertain significance Fanconi anemia 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 207 of the FANCC protein (p.His207Leu). This variant is present in population databases (rs202038890, gnomAD 0.004%). This missense change has been observed in individual(s) with breast cancer and serous cystadenoma (PMID: 23028338, 28767289). ClinVar contains an entry for this variant (Variation ID: 409651). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on FANCC protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000480838 SCV000564975 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 23028338, 28767289, Gordon2000[Book])
Fulgent Genetics, Fulgent Genetics RCV000766067 SCV000897538 uncertain significance Fanconi anemia complementation group C 2022-03-16 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000469377 SCV002535113 uncertain significance Fanconi anemia 2021-05-07 criteria provided, single submitter curation
Ambry Genetics RCV002365644 SCV002658146 uncertain significance Hereditary cancer-predisposing syndrome 2022-06-03 criteria provided, single submitter clinical testing The p.H207L variant (also known as c.620A>T), located in coding exon 6 of the FANCC gene, results from an A to T substitution at nucleotide position 620. The histidine at codon 207 is replaced by leucine, an amino acid with similar properties. This alteration has been reported in a cohort of breast cancer families (Thompson ER et al. PLoS Genet., 2012 Sep;8:e1002894). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000469377 SCV002081241 uncertain significance Fanconi anemia 2018-09-17 no assertion criteria provided clinical testing

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