ClinVar Miner

Submissions for variant NM_000136.3(FANCC):c.689_691AGA[1] (p.Lys231del) (rs3831244)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000160467 SCV000211032 uncertain significance not provided 2017-03-23 criteria provided, single submitter clinical testing This in frame deletion of 3 nucleotides is denoted FANCC c.692_694delAGA at the cDNA level and p.Lys231del (K231del) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AAGA[delAGA]TTTC. This deletion of a single Lysine residue occurs in a region which is conserved across species and is located in the region of interaction with GRP94 and Hsp70 (Gordon 2000). This variant was observed in the heterozygous state in an individual with Fanconi Anemia and was classified as having uncertain significance (De Rocco 2014). Since in frame deletions may or may not inhibit proper protein functioning, the clinical significance of this finding remains unclear at this time and we consider FANCC Lys231del to be a variant of uncertain significance.
Invitae RCV000470311 SCV000549950 uncertain significance Fanconi anemia 2018-05-25 criteria provided, single submitter clinical testing This sequence change deletes 3 nucleotides from exon 8 of the FANCC mRNA (c.692_694delAGA). This leads to the deletion of 1 amino acid residue in the FANCC protein (p.Lys231del) but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs3831244, ExAC 0.005%). This variant has been observed on the opposite chromosome (in trans) from a pathogenic variant in an individual affected with Fanconi anemia (PMID: 24584348). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 182466). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the deleted amino acid is currently unknown. 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.

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