ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2204C>T (p.Thr735Ile)

dbSNP: rs1596235743
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001014760 SCV001175512 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-03 criteria provided, single submitter clinical testing The p.T735I variant (also known as c.2204C>T), located in coding exon 9 of the BLM gene, results from a C to T substitution at nucleotide position 2204. The threonine at codon 735 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV002550798 SCV002984859 uncertain significance Bloom syndrome 2022-07-29 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 735 of the BLM protein (p.Thr735Ile). 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: 820880). 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"). RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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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