ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1328A>G (p.Asn443Ser)

gnomAD frequency: 0.00013  dbSNP: rs139343938
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001566516 SCV001790048 uncertain significance not provided 2020-07-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Invitae RCV001566516 SCV002188609 uncertain significance not provided 2021-09-08 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 443 of the TPP1 protein (p.Asn443Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs139343938, ExAC 0.03%). This variant has not been reported in the literature in individuals affected with TPP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 457938). 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.
Ambry Genetics RCV002527680 SCV003742009 uncertain significance Inborn genetic diseases 2022-12-06 criteria provided, single submitter clinical testing The c.1328A>G (p.N443S) alteration is located in exon 11 (coding exon 11) of the TPP1 gene. This alteration results from a A to G substitution at nucleotide position 1328, causing the asparagine (N) at amino acid position 443 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001834751 SCV002094814 uncertain significance Neuronal ceroid lipofuscinosis 2 2019-11-11 no assertion criteria provided clinical testing

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