ClinVar Miner

Submissions for variant NM_006172.4(NPPA):c.253G>A (p.Gly85Arg) (rs749353276)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000233070 SCV000289142 uncertain significance Atrial fibrillation, familial, 6 2016-03-07 criteria provided, single submitter clinical testing This sequence change replaces glycine with arginine at codon 85 of the NPPA protein (p.Gly85Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is present in population databases (rs749353276, ExAC 0.04%) but has not been reported in the literature in individuals with a NPPA-related disease. 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. In addition, the arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. However, algorithms developed to predict the effect of nucleotide changes on mRNA splicing suggest that this variant may alter mRNA splicing, but these predictions have not been confirmed by published transcriptional studies. In summary, this is a rare missense change with an uncertain impact on mRNA splicing. It has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000764958 SCV000896132 uncertain significance Atrial fibrillation, familial, 6; Atrial standstill 2 2018-10-31 criteria provided, single submitter clinical testing

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