ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1057_1058del (p.Met353fs)

dbSNP: rs886044829
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725465 SCV000337129 pathogenic not provided 2015-10-30 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000362601 SCV000695726 likely pathogenic Fabry disease 2016-06-02 criteria provided, single submitter clinical testing Variant summary: The GLA c.1057_1058delAT (p.Met353Aspfs) variant results in a premature termination codon, predicted to cause a truncated or absent GLA protein, which are commonly known mechanisms for disease. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP) and has been reported in one affected individual via a publication. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as a "Probable Disease Variant/Likely Pathogenic," until additional information becomes available.
Genome-Nilou Lab RCV000362601 SCV002054379 pathogenic Fabry disease 2021-07-15 criteria provided, single submitter clinical testing
Invitae RCV000362601 SCV002242473 pathogenic Fabry disease 2021-06-24 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the C-terminus of the GLA protein. Other variant(s) that disrupt this region (p.Tyr397Metfs*7) have been determined to be pathogenic (PMID: 10666480). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. This variant has been observed in individual(s) with Fabry disease (PMID: 9100224). ClinVar contains an entry for this variant (Variation ID: 284485). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Met353Aspfs*21) in the GLA gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 77 amino acid(s) of the GLA protein.

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