ClinVar Miner

Submissions for variant NM_000135.4(FANCA):c.1308G>C (p.Gln436His)

dbSNP: rs1316078638
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378190 SCV001575701 likely pathogenic Fanconi anemia 2020-10-23 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Gln436 amino acid residue in FANCA. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 29098742). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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) performed at Invitae indicates that this missense variant is expected to disrupt FANCA protein function. This variant has not been reported in the literature in individuals with FANCA-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with histidine at codon 436 of the FANCA protein (p.Gln436His). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and histidine.

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