ClinVar Miner

Submissions for variant NM_000487.6(ARSA):c.677C>T (p.Ala226Val) (rs74315468)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000343115 SCV000338915 uncertain significance not provided 2016-10-27 criteria provided, single submitter clinical testing
Invitae RCV000003217 SCV000752524 likely pathogenic Metachromatic leukodystrophy 2019-08-26 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 226 of the ARSA protein (p.Ala226Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has been reported as in combination with another ARSA variant in an individual affected with metachromatic leukodystrophy (PMID: 7906588, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also know as A224V in the literature. ClinVar contains an entry for this variant (Variation ID: 3071). 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: Probably Damaging; 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 RCV000003217 SCV000023375 pathogenic Metachromatic leukodystrophy 1993-12-01 no assertion criteria provided literature only

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