ClinVar Miner

Submissions for variant NM_000021.4(PSEN1):c.118_120del (p.Asp40del)

dbSNP: rs759538127
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002004172 SCV002291635 uncertain significance Alzheimer disease 3; Frontotemporal dementia; Pick disease; Acne inversa, familial, 3 2023-09-27 criteria provided, single submitter clinical testing Experimental studies have shown that this variant affects PSEN1 function (PMID: 27930341, 32087291). This variant, c.118_120del, results in the deletion of 1 amino acid(s) of the PSEN1 protein (p.Asp40del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs759538127, gnomAD 0.03%). This variant has been observed in individual(s) with clinical features of Alzheimer disease (PMID: 24463146, 32917274, 35949106). ClinVar contains an entry for this variant (Variation ID: 1505666). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. 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.
PreventionGenetics, part of Exact Sciences RCV003395351 SCV004120020 uncertain significance PSEN1-related disorder 2024-09-10 no assertion criteria provided clinical testing The PSEN1 c.118_120delGAC variant is predicted to result in an in-frame deletion (p.Asp40del). This variant has been found in a patient with early onset Alzheimer disease, but no further segregation study was performed (Nygaard et al. 2014. PubMed ID: 24463146). This variant may affect the protein function, but the pathogenicity of the variant has not been elucidated (Sun et al. 2017. PubMed ID: 27930341; Perrone et al. 2020. PubMed ID: 32917274). This variant is reported in 0.033% of alleles in individuals of South Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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