ClinVar Miner

Submissions for variant NM_000027.4(AGA):c.792G>A (p.Met264Ile)

gnomAD frequency: 0.00034  dbSNP: rs369967348
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001280247 SCV002201774 uncertain significance Aspartylglucosaminuria 2022-08-21 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 264 of the AGA protein (p.Met264Ile). This variant is present in population databases (rs369967348, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with AGA-related conditions. ClinVar contains an entry for this variant (Variation ID: 991946). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV001280247 SCV002812238 uncertain significance Aspartylglucosaminuria 2021-07-12 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587108 SCV005077409 uncertain significance not specified 2024-04-05 criteria provided, single submitter clinical testing Variant summary: AGA c.792G>A (p.Met264Ile) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251496 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in AGA causing Aspartylglucosaminuria (0.00012 vs 0.0049), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.792G>A in individuals affected with Aspartylglucosaminuria and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 991946). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001280247 SCV001467411 uncertain significance Aspartylglucosaminuria 2020-04-16 no assertion criteria provided clinical testing

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