Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323773 | SCV004029027 | uncertain significance | not specified | 2023-07-21 | criteria provided, single submitter | clinical testing | Variant summary: PYCR1 c.866A>G (p.Lys289Arg) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 8e-06 in 250368 control chromosomes (gnomAD v2.1 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.866A>G has been reported in the literature in at least one homozygous individual affected with Cutis Laxa (e.g., Alfares_2017). These data indicate that the variant may be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function, finding that the variant results in increased enzymatic activity relative to wild type, however, it is unclear how this variant effect may contribute to Cutis Laxa disease (e.g., Chen_2019). The following publications have been ascertained in the context of this evaluation (PMID: 28454995, 31108370). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Biochemical Molecular Genetic Laboratory, |
RCV000985197 | SCV001133220 | likely pathogenic | Autosomal recessive cutis laxa type 2B | 2019-09-26 | no assertion criteria provided | clinical testing |