Submissions for variant NM_000036.3(AMPD1):c.1365G>A (p.Trp455Ter)

dbSNP: rs1447749222

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523515	SCV000619868	likely pathogenic	not provided	2017-08-08	criteria provided, single submitter	clinical testing	The W488X variant in the AMPD1 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The W488X variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). We interpret W488X as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002525198	SCV003346773	uncertain significance	Muscle AMP deaminase deficiency	2022-06-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp488*) in the AMPD1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in AMPD1 cause disease. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AMPD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 451200). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.