ClinVar Miner

Submissions for variant NM_007375.4(TARDBP):c.962C>A (p.Ala321Asp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001207766 SCV001379132 uncertain significance Amyotrophic lateral sclerosis type 10; TARDBP-related frontotemporal dementia 2019-10-16 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 321 of the TARDBP protein (p.Ala321Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TARDBP-related conditions. 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: "Benign"; Align-GVGD: "Class C65"). This variant disrupts the p.Ala321 amino acid residue in TARDBP. Other variant(s) that disrupt this residue have been observed in individuals with TARDBP-related conditions (PMID: 19760257, 19864663), which suggests that this may be a clinically significant amino acid residue. 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.

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