ClinVar

Description

The identified heterozygous variant (c.1501+1G>A) lies in an essential splice donor site downstream of exon 7 of the HNF1A gene. In silico splice prediction tools (NNSPLICE and ASSP) predict that this variant is likely to disrupt the splice site at the junction of exon 7 and intron 7 of the HNF1A gene. This could lead to a frameshift, which will probably result in truncation of the protein. Moreover, due to introduction of premature stop codon, this aberrant transcript will likely be targeted by nonsense mediated mRNA decay (NMD) mechanism. The identified variant seems to be a novel, as it has not been previously reported in literature nor previously identified by our laboratory. However, another splice site variant occurring at the same position as that of the identified variant, c.1501+1G>T has been previously reported in a South-Brazilian patient affected with MODY and was predicted abolish the splice donor site resulting in the generation of abnormal transcripts [PMID: 19169489]. The identified variant disrupts an essential splice site and is likely to result in a truncated protein. In addition, it lies in the vicinity of other variants associated with MODY. Thus, it has been labelled as 'likely pathogenic' (likely disease-causing).