Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002512685 | SCV003443360 | pathogenic | not provided | 2022-10-03 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg288*) in the FERMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in FERMT1 are known to be pathogenic (PMID: 14962093, 21936020). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Kindler syndrome (PMID: 12789646). ClinVar contains an entry for this variant (Variation ID: 2718). For these reasons, this variant has been classified as Pathogenic. |
Molecular Genetics, |
RCV000002837 | SCV004812587 | pathogenic | Kindler syndrome | 2022-03-03 | criteria provided, single submitter | clinical testing | This sequence change in FERMT1 is a nonsense variant predicted to cause a premature stop codon, p.(Arg288*), in biologically-relevant-exon 7/15 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PMID: 26937547). The highest population minor allele frequency in gnomAD v3.1 is 0.002% (1/41,324 alleles) in the African/African American population, which is consistent with recessive disease. This variant has been detected homozygous in at least three individuals with Kindler syndrome from unrelated consanguineous families (PMID: 12789646, 24635075). Based on the classification scheme RMH Modified ACMG Guidelines v1.5.1, this variant is classified as PATHOGENIC. Following criteria are met: PVS1, PM2_Supporting, PM3_Supporting. |
OMIM | RCV000002837 | SCV000022995 | pathogenic | Kindler syndrome | 2003-07-01 | no assertion criteria provided | literature only | |
Gene |
RCV000002837 | SCV000265623 | not provided | Kindler syndrome | no assertion provided | literature only | Common pathogenic variant |