ClinVar Miner

Submissions for variant NM_024312.5(GNPTAB):c.1363G>T (p.Ala455Ser)

gnomAD frequency: 0.00001  dbSNP: rs137853822
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000666169 SCV000790416 uncertain significance Mucolipidosis type II; Pseudo-Hurler polydystrophy 2017-03-20 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002271552 SCV002555906 uncertain significance not specified 2022-06-15 criteria provided, single submitter clinical testing Variant summary: GNPTAB c.1363G>T (p.Ala455Ser) results in a conservative amino acid change located in the Notch domain (IPR000800) of 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 8e-06 in 251452 control chromosomes (gnomAD). c.1363G>T has been reported in the literature in at least one individual affected with stuttering (example: Kang_2010). A different variant affecting the same residue has been observed in two compound heterozygous individuals in one family (c.1364C>T, p.A455V and IVS13+1G>A) affected with Mucolipidosis and the variant segregated with disease (Yu_2019), suggesting that it is a clinically significant residue. In addition, Han_2019 showed this variant produces vocalization deficit in 8-day-old pup isolation calls and does not affect other nonvocal behaviors in mouse model. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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