Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089978 | SCV001245031 | uncertain significance | Mitochondrial myopathy-lactic acidosis-deafness syndrome | 2018-12-17 | criteria provided, single submitter | clinical testing | A homozygous missense variant, NM_015723.3(PNPLA8):c.2161G>A, has been identified in exon 12 of 12 of the PNPLA8 gene. The variant is predicted to result in a minor amino acid change from glutamic acid to lysine at position 721 of the protein (NP_056538.1(PNPLA8):p.(Glu721Lys)). The glutamic acid residue at this position has very high conservation (100 vertebrates, UCSC), but is not located within a well established functional domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). This variant has not been previously reported in clinical cases. Analysis of parental samples indicated this variant was paternally and maternally inherited. Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS). |