Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002512620 | SCV003441701 | pathogenic | not provided | 2022-08-21 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr439*) in the LMF1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMF1 are known to be pathogenic (PMID: 17994020, 19820022, 22239554). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with combined lipase deficiency (PMID: 17994020). ClinVar contains an entry for this variant (Variation ID: 792). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this premature translational stop signal affects LMF1 function (PMID: 17994020). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000000828 | SCV000020978 | pathogenic | Lipase deficiency, combined | 2007-12-01 | no assertion criteria provided | literature only | |
GBinsight Genetic Testing by GB Health |
RCV000000828 | SCV001314173 | pathogenic | Lipase deficiency, combined | 2020-05-27 | no assertion criteria provided | clinical testing | Proband referred for clinical genetic testing presented with syndrome consistent with familial chylomicronemia syndrome with severe hypertriglyceridemia, low HDL-cholesterol and type 2 diabetes. Clinical genetic testing identified homozygosity for the Cys77Tyr (NM_178172.6:c.230G>A) genetic variant in the the germline. Phenotype segregated with genotype in family members. This variant introduces a premature stop codon, which can cause nonsense-mediated decay of the mutant protein. Péterfy et al (PMID: 17994020) identified this genetic variant in patients with severe hypertriglyceridemia and classified this variant as pathogenic for LMF1 deficiency. |