ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1036del (p.Ala346fs) (rs1555900463)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667899 SCV000792418 likely pathogenic Metachromatic leukodystrophy 2017-06-23 criteria provided, single submitter clinical testing
Invitae RCV000667899 SCV001220569 likely pathogenic Metachromatic leukodystrophy 2019-01-30 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the ARSA gene (p.Ala346Leufs*77). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 164 amino acids of the ARSA protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with ARSA-related conditions. ClinVar contains an entry for this variant (Variation ID: 552604). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant disrupts the p.Glu384 amino acid residue in ARSA. Other variant(s) that disrupt this residue have been observed in individuals with ARSA-related conditions (PMID: 26462614, 7906588, 15375602, 20339381, 19021637), suggesting that it is a clinically significant residue. As a result, variants that disrupt this residue are likely to be causative of disease. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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