NM_000487.6(ARSA):c.1087dup (p.Leu363fs) AND Metachromatic leukodystrophy

Clinical significance:Pathogenic (Last evaluated: Feb 8, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000487.6(ARSA):c.1087dup (p.Leu363fs)]

NM_000487.6(ARSA):c.1087dup (p.Leu363fs)

ARSA:arylsulfatase A [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000487.6(ARSA):c.1087dup (p.Leu363fs)
  • NC_000022.11:g.50625960dup
  • NG_009260.2:g.7224dup
  • NM_000487.6:c.1087dupMANE SELECT
  • NM_001085425.3:c.1087dup
  • NM_001085426.3:c.1087dup
  • NM_001085427.3:c.1087dup
  • NM_001085428.3:c.829dup
  • NM_001362782.2:c.829dup
  • NP_000478.3:p.Leu363fs
  • NP_001078894.2:p.Leu363fs
  • NP_001078895.2:p.Leu363fs
  • NP_001078896.2:p.Leu363fs
  • NP_001078897.1:p.Leu277fs
  • NP_001349711.1:p.Leu277fs
  • NC_000022.10:g.51064383_51064384insG
  • NC_000022.10:g.51064388dup
  • NM_000487.5:c.1087dup
Protein change:
Molecular consequence:
  • NM_000487.6:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001085425.3:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001085426.3:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001085427.3:c.1087dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001085428.3:c.829dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001362782.2:c.829dup - frameshift variant - [Sequence Ontology: SO:0001589]


Metachromatic leukodystrophy (MLD)
Metachromatic leukoencephalopathy; Sulfatide lipidosis; Cerebral sclerosis diffuse metachromatic form; See all synonyms [MedGen]
MONDO: MONDO:0018868; MedGen: C0023522; Orphanet: 512; OMIM: 250100

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001229158Invitaecriteria provided, single submitter
(Feb 8, 2019)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Mutation Update of ARSA and PSAP Genes Causing Metachromatic Leukodystrophy.

Cesani M, Lorioli L, Grossi S, Amico G, Fumagalli F, Spiga I, Filocamo M, Biffi A.

Hum Mutat. 2016 Jan;37(1):16-27. doi: 10.1002/humu.22919. Epub 2015 Nov 4. Review.

PubMed [citation]

Missense mutations in the arylsulphatase A genes of metachromatic leukodystrophy patients.

Barth ML, Fensom A, Harris A.

Hum Mol Genet. 1993 Dec;2(12):2117-21.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001229158.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)


This sequence change results in a premature translational stop signal in the ARSA gene (p.Leu363Profs*47). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 147 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. 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 C-terminus of the ARSA protein. Another variant that disrupts this region (p.Pro349Hisfs*74) has been determined to be pathogenic (PMID:26462614, 7906588, 19021637, 10220151). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. For these reasons, this variant has been classified as Pathogenic.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 7, 2021

Support Center