ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.1138G>A (p.Ala380Thr) (rs190013230)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000764998 SCV000896181 uncertain significance Ceroid lipofuscinosis neuronal 2; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000189783 SCV000243431 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing p.Ala380Thr (GCC>ACC): c.1138 G>A in exon 9 of the TPP1 gene (NM_000391.3)The Ala380Thr missense change has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The amino acid substitution is non-conservative, as a non-polar Alanine residue is replaced by a polar Threonine residue. It alters a highly conserved position in the protein, and other missense mutations have been reported at nearby residues. Some in silico algorithms predict it may be damaging to protein structure/function while other suggest it may be benign. Therefore, based on the currently available information, it is unclear whether Ala380Thr is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).

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