ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.1229C>T (p.Thr410Ile) (rs28940895)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001376978 SCV001574193 likely pathogenic Metachromatic leukodystrophy 2020-08-20 criteria provided, single submitter clinical testing This sequence change replaces threonine with isoleucine at codon 410 of the ARSA protein (p.Thr410Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is present in population databases (rs28940895, ExAC 0.002%). This variant has been observed in individual(s) with metachromatic leukodystrophy (PMID: 11456299). It has also been observed to segregate with disease in related individuals. This variant is also known as Thr408Ile in the literature. ClinVar contains an entry for this variant (Variation ID: 3092). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Benign; Align-GVGD: Class C0). 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.
OMIM RCV000003238 SCV000023396 pathogenic Metachromatic leukodystrophy, adult type 2001-07-01 no assertion criteria provided literature only

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