ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1583C>T (p.Thr528Ile)

dbSNP: rs1596230185
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001012284 SCV001172716 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-03 criteria provided, single submitter clinical testing The c.1583C>T (p.T528I) alteration is located in exon 7 (coding exon 6) of the BLM gene. This alteration results from a C to T substitution at nucleotide position 1583, causing the threonine (T) at amino acid position 528 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001204243 SCV001375442 uncertain significance Bloom syndrome 2022-04-08 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 528 of the BLM protein (p.Thr528Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 819598). 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.
GeneDx RCV002284455 SCV002574148 uncertain significance not provided 2022-03-16 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Quest Diagnostics Nichols Institute San Juan Capistrano RCV002284455 SCV005624237 uncertain significance not provided 2024-11-26 criteria provided, single submitter clinical testing The BLM c.1583C>T (p.Thr528Ile) variant has not been reported in individuals with BLM-related conditions in the published literature. It also has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV001204243 SCV002092373 uncertain significance Bloom syndrome 2019-02-06 no assertion criteria provided clinical testing

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