ClinVar Miner

Submissions for variant NM_015665.6(AAAS):c.1191dup (p.Glu398fs)

gnomAD frequency: 0.00003  dbSNP: rs746305979
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000494064 SCV000582138 pathogenic not provided 2024-06-06 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 31589614, 11159947, 12429595)
Fulgent Genetics, Fulgent Genetics RCV001782989 SCV002797358 pathogenic Glucocorticoid deficiency with achalasia 2022-05-13 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000494064 SCV003440540 pathogenic not provided 2024-02-05 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu398Argfs*28) in the AAAS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in AAAS are known to be pathogenic (PMID: 11159947). This variant is present in population databases (rs746305979, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with achalasia-addisonianism-alacrimia syndrome (PMID: 12429595). This variant is also known as 1273 Ins A. ClinVar contains an entry for this variant (Variation ID: 429542). For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV003962360 SCV004785665 pathogenic AAAS-related disorder 2023-12-20 no assertion criteria provided clinical testing The AAAS c.1191dupA variant is predicted to result in a frameshift and premature protein termination (p.Glu398Argfs*28). This variant was reported in the compound heterozygous state with a known causative AAAS variant in an individual with Triple-A syndrome (described as 1273 Ins A in Family 2, Houlden et al. 2002. PubMed ID: 12429595). This variant is reported in 0.020% of alleles in individuals of Latino descent in gnomAD. Frameshift variants in AAAS are expected to be pathogenic. This variant is interpreted as pathogenic.

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