ClinVar Miner

Submissions for variant NM_000262.3(NAGA):c.230T>C (p.Ile77Thr)

gnomAD frequency: 0.00011  dbSNP: rs375884363
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001347328 SCV001541584 uncertain significance Alpha-N-acetylgalactosaminidase deficiency type 1 2021-09-01 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 77 of the NAGA protein (p.Ile77Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs375884363, ExAC 0.02%). This variant has not been reported in the literature in individuals affected with NAGA-related conditions. 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: "Probably 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004782720 SCV005394913 uncertain significance not specified 2024-09-11 criteria provided, single submitter clinical testing Variant summary: NAGA c.230T>C (p.Ile77Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 250822 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.230T>C in individuals affected with Kanzaki Disease and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 1043247). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV004960832 SCV005458740 uncertain significance Inborn genetic diseases 2024-11-20 criteria provided, single submitter clinical testing The c.230T>C (p.I77T) alteration is located in exon 3 (coding exon 3) of the NAGA gene. This alteration results from a T to C substitution at nucleotide position 230, causing the isoleucine (I) at amino acid position 77 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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