Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000505674 | SCV000826155 | likely pathogenic | Hyperprolinemia type 2 | 2021-08-31 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000505674 | SCV000914371 | uncertain significance | Hyperprolinemia type 2 | 2018-11-19 | criteria provided, single submitter | clinical testing | The ALDH4A1 c.866+1G>A variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. It was observed by ICSL 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 for this variant, it 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 and cDNA change. No publications were found based on this search. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for hyperprolinemia. |
Baylor Genetics | RCV000505674 | SCV001521274 | likely pathogenic | Hyperprolinemia type 2 | 2019-12-19 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. |
Donald Williams Parsons Laboratory, |
RCV000505674 | SCV000599974 | pathogenic | Hyperprolinemia type 2 | 2014-11-17 | no assertion criteria provided | research | This splice site variant is categorized as deleterious according to ACMG guidelines (PMID:18414213). It would be pathogenic in a recessive state; heterozygotes would be carriers for the condition. It was found once in our study heterozygous, maternally inherited in a 12-year-old female with pilocytic astrocytoma and intellectual disability. |