ClinVar Miner

Submissions for variant NM_176787.5(PIGN):c.1697A>G (p.Tyr566Cys)

gnomAD frequency: 0.00001  dbSNP: rs540784458
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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 RCV001222770 SCV001394886 uncertain significance Multiple congenital anomalies-hypotonia-seizures syndrome 1 2021-08-28 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 566 of the PIGN protein (p.Tyr566Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is present in population databases (rs540784458, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with PIGN-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The cysteine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
GeneDx RCV003127698 SCV003803545 uncertain significance not provided 2023-12-29 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004032451 SCV005005589 uncertain significance Inborn genetic diseases 2023-10-02 criteria provided, single submitter clinical testing The c.1697A>G (p.Y566C) alteration is located in exon 19 (coding exon 16) of the PIGN gene. This alteration results from a A to G substitution at nucleotide position 1697, causing the tyrosine (Y) at amino acid position 566 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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