ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1303C>T (p.Arg435Cys) (rs148473140)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671453 SCV000796429 likely pathogenic Fanconi anemia, complementation group A 2017-12-14 criteria provided, single submitter clinical testing
Invitae RCV000805493 SCV000945450 pathogenic Fanconi anemia 2018-10-29 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 435 of the FANCA protein (p.Arg435Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148473140, ExAC 0.01%). This variant has been observed in the compound heterozygous state in several individuals affected with Fanconi anemia (PMID: 28102861, 15523645). ClinVar contains an entry for this variant (Variation ID: 555603). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Arg435 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 19367192, Invitae), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

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