ClinVar Miner

Submissions for variant NM_001365068.1(ASTN2):c.2806+26381A>G (rs752860146)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000267091 SCV000343087 uncertain significance not provided 2018-08-15 criteria provided, single submitter clinical testing
Broad Institute Rare Disease Group, Broad Institute RCV001004955 SCV001164487 uncertain significance Sarcotubular myopathy 2018-12-03 criteria provided, single submitter research The heterozygous p.Phe550Leu variant in TRIM32 was identified by our study in the compound heterozygous state, with a VUS, in one individual with limb-girdle muscular dystrophy (LGMD). This variant has been identified in 0.002690% (3/111516) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs121434447). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Phe550Leu is uncertain. ACMG/AMP Criteria applied: PM2 (Richards 2015).
Invitae RCV001301092 SCV001490252 uncertain significance Bardet-Biedl syndrome 2018-06-21 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 550 of the TRIM32 protein (p.Phe550Leu). The phenylalanine residue is highly conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is present in population databases (rs752860146, ExAC 0.001%). This variant has not been reported in the literature in individuals with TRIM32-related disease. ClinVar contains an entry for this variant (Variation ID: 288854). 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 C1). 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. 5

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