Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000404090 | SCV000446692 | uncertain significance | Abetalipoproteinaemia | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Department of Pathology and Laboratory Medicine, |
RCV000404090 | SCV001552214 | likely pathogenic | Abetalipoproteinaemia | no assertion criteria provided | clinical testing | The MTTP p.Ser32* variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs886058955) and ClinVar (classified as a VUS by Illumina for abetalipoproteinemia). The variant was also identified in control databases in 4 of 130842 chromosomes at a frequency of 0.000031 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (Finnish) in 1 of 5388 chromosomes (freq: 0.000186) and Latino in 3 of 24356 chromosomes (freq: 0.000123); it was not observed in the African, Ashkenazi Jewish, East Asian, European (non-Finnish), Other or South Asian populations. The p.Ser32* variant leads to a premature stop codon at position 32 which may lead to a truncated or absent protein and loss of function. Loss of function variants of the MTTP gene are an established mechanism of disease in Abetalipoproteinemia and is the type of variant expected to cause the disorder when found in the homozygous or compound heterozygous state. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more pathogenic role for this variant. This variant is classified as likely pathogenic. |