Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003317034 | SCV004020893 | likely pathogenic | Metachromatic leukodystrophy | 2023-06-09 | criteria provided, single submitter | clinical testing | Variant summary: PSAP c.1046T>C (p.Leu349Pro) results in a non-conservative amino acid change located in the Saposin-like type B, region 1 domain (IPR007856) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251204 control chromosomes. c.1046T>C has been reported in the literature in adult compound heterozygous individuals affected with Gaucher disease with saposin C deficiency, including two affected siblings from the same family (example: Tylki-Syzmanska_2007, DAmore_2021). At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in ~50%-90% of normal activity, with results suggestive of a mild disease course (example: Motta_2014). The following publications have been ascertained in the context of this evaluation (PMID: 34649574, 24925315, 17919309, 20484222). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| OMIM | RCV000014301 | SCV000034550 | pathogenic | Gaucher disease due to saposin C deficiency | 2007-12-01 | no assertion criteria provided | literature only |