Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000410209 | SCV000485417 | likely pathogenic | Metachromatic leukodystrophy | 2015-12-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000410209 | SCV001360432 | likely pathogenic | Metachromatic leukodystrophy | 2019-08-29 | criteria provided, single submitter | clinical testing | Variant summary: ARSA c.211_212delTG (p.Cys71HisfsX4) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.304delC, p.Leu102fsX6; c.960G>A, p.Trp320X). The variant was absent in 168270 control chromosomes (gnomAD). The variant, c.211_212delTG, has been reported in the literature in one homozygous individual affected with Metachromatic Leukodystrophy (Eng_2003). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One ClinVar submission from other clinical diagnostic laboratories (evaluation after 2014) cited the variant once as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Invitae | RCV000410209 | SCV001589206 | pathogenic | Metachromatic leukodystrophy | 2022-12-15 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with metachromatic leukodystrophy (PMID: 14517960). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Cys71Hisfs*4) 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 also known as c.205_206delTG (p.Cys69fs). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370171). |