Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410367 | SCV000486176 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | 2016-04-11 | criteria provided, single submitter | clinical testing | |
Invitae | RCV002523858 | SCV003230520 | pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370774). This variant has not been reported in the literature in individuals affected with LAMB3-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1012*) in the LAMB3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMB3 are known to be pathogenic (PMID: 11023379, 16473856). |
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RCV000410367 | SCV003926491 | likely pathogenic | Junctional epidermolysis bullosa gravis of Herlitz | criteria provided, single submitter | clinical testing | A Homozygote Nonsense variant c.3034C>T in Exon 20 of the LAMB3 gene that results in the amino acid substitution p.Gln1012* was identified. The observed variant has a maximum allele frequency of 0% in gnomAD exomes and genomes, respectively. The severity of the impact of this variant on the protein is high, based on the effect of the protein and REVEL score. Rare Exome Variant Ensemble Learner (REVEL) is an ensembl method for predicting the pathogenicity of missense variants based on a combination of scores from 13 individual tools: MutPred, FATHMM v2.3, VEST 3.0, PolyPhen-2, SIFT, PROVEAN, MutationAssessor, MutationTaster, LRT, GERP++, SiPhy, phyloP, and phastCons. The REVEL score for an individual missense variant can range from 0 to 1, with higher scores reflecting greater likelihood that the variant is disease-causing. ClinVar has also classified this variant as Likely Pathogenic with 1 star, criteria provided, single submitter (variant ID: 370774). Based on the above evidence this variant has been classified as Likely Pathogenic according to the ACMG guidelines. |