ClinVar Miner

Submissions for variant NM_000303.3(PMM2):c.178G>T (p.Val60Leu) (rs759513930)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000636240 SCV000757673 uncertain significance Carbohydrate-deficient glycoprotein syndrome type I 2018-06-27 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 60 of the PMM2 protein (p.Val60Leu). The valine residue is highly conserved and there is a small physicochemical difference between valine and leucine. This variant also falls at the last nucleotide of exon 2 of the PMM2 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs759513930, ExAC 0.04%). This variant has been observed in an individual with clinical features and biochemical testing consistent with PMM2-related disease (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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 RCV000636240 SCV000896574 uncertain significance Carbohydrate-deficient glycoprotein syndrome type I 2018-10-31 criteria provided, single submitter clinical testing

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