Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588032 | SCV000696812 | pathogenic | Metachromatic leukodystrophy | 2017-03-09 | criteria provided, single submitter | clinical testing | Variant summary: The ARSA c.960G>A (p.Trp320X) variant results in a premature termination codon, predicted to cause a truncated or absent ARSA protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Multiple publications have cited the variant in affected individuals (varying degrees of onset: late-infantile, juvenile, and adult), who were compound heterozygotes or homozygotes, with significantly lower to nondetectable ARSA enzymatic activity. Therefore, the variant of interest has been classified as "pathogenic." |
Invitae | RCV000588032 | SCV002237778 | pathogenic | Metachromatic leukodystrophy | 2023-08-04 | criteria provided, single submitter | clinical testing | This variant is also known as W318X. This sequence change creates a premature translational stop signal (p.Trp320*) in the ARSA gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ARSA are known to be pathogenic (PMID: 8962139, 10477432). This variant is present in population databases (no rsID available, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with metachromatic leukodystrophy (PMID: 11020646, 26553228, 30057904). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 495883). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000588032 | SCV002810932 | pathogenic | Metachromatic leukodystrophy | 2022-05-13 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000588032 | SCV001132334 | likely pathogenic | Metachromatic leukodystrophy | 2015-03-25 | no assertion criteria provided | clinical testing |