ClinVar Miner

Submissions for variant NM_000169.3(GLA):c.1A>G (p.Met1Val)

dbSNP: rs869312265
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Revvity Omics, Revvity RCV001783375 SCV002021897 pathogenic not provided 2020-07-01 criteria provided, single submitter clinical testing
Ambry Genetics RCV003375362 SCV004095610 likely pathogenic Cardiovascular phenotype 2023-07-06 criteria provided, single submitter clinical testing The p.M1? variant (also known as c.1A>G) is located in coding exon 1 of the GLA gene and results from a A to G substitution at nucleotide position 1. This alters the methionine residue at the initiation codon (ATG). This alteration has been reported in individuals with Fabry disease (Liguori R et al. PLoS One. 2017 Jul 3;12(7):e0180581; Paz et al. J Bras Nefrol. 2023 Feb 6:S0101-28002023005005502). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is not well conserved in available vertebrate species. In addition to the clinical data presented in the literature, sequence variations that modify the initiation codon are expected to result in either loss of translation initiation, N-terminal truncation, or cause a shift in the mRNA reading frame. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003509694 SCV004299657 pathogenic Fabry disease 2023-11-03 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the GLA mRNA. The next in-frame methionine is located at codon 42. This variant is not present in population databases (gnomAD no frequency). Disruption of the initiator codon has been observed in individual(s) with Fabry disease (PMID: 8807334, 12175777, 27896102, 28275245, 28672034, 31372342). ClinVar contains an entry for this variant (Variation ID: 1323011). For these reasons, this variant has been classified as Pathogenic.

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