ClinVar Miner

Submissions for variant NM_000204.5(CFI):c.1176_1177dup (p.Trp393fs)

dbSNP: rs758049059
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000400152 SCV000330032 pathogenic not provided 2022-12-06 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12562389)
Labcorp Genetics (formerly Invitae), Labcorp RCV000400152 SCV001231440 pathogenic not provided 2023-12-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp393Tyrfs*5) in the CFI gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CFI are known to be pathogenic (PMID: 15917334, 16621965, 19065647, 20016463, 22710145). This variant is present in population databases (rs758049059, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with complement factor I deficiency (PMID: 12562389, 22710145). It has also been observed to segregate with disease in related individuals. This variant is also known as 1205insAT. ClinVar contains an entry for this variant (Variation ID: 280145). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002500970 SCV002809714 pathogenic Atypical hemolytic-uremic syndrome with I factor anomaly; Age related macular degeneration 13; Factor I deficiency 2021-07-06 criteria provided, single submitter clinical testing
OMIM RCV002266943 SCV000033144 pathogenic Factor I deficiency 2003-02-01 no assertion criteria provided literature only
PreventionGenetics, part of Exact Sciences RCV004535248 SCV004715536 pathogenic CFI-related disorder 2023-12-04 no assertion criteria provided clinical testing The CFI c.1176_1177dupAT variant is predicted to result in a frameshift and premature protein termination (p.Trp393Tyrfs*5). This variant was reported in the homozygous state in two siblings with complement factor I deficiency (Baracho et al. 2003. PubMed ID: 12562389, reported as 1204_1205insAT). This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-110667629-C-CAT). Frameshift variants in CFI are expected to be pathogenic. This variant is interpreted as pathogenic.

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