ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3535del (p.Thr1179fs)

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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 RCV003076378 SCV003450493 pathogenic Bloom syndrome 2023-08-10 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 2142715). This premature translational stop signal has been observed in individual(s) with Bloom syndrome (PMID: 34538859). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr1179Leufs*3) in the BLM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155).
Ambry Genetics RCV003348997 SCV004051464 pathogenic Hereditary cancer-predisposing syndrome 2023-06-27 criteria provided, single submitter clinical testing The c.3535delA pathogenic mutation, located in coding exon 17 of the BLM gene, results from a deletion of one nucleotide at nucleotide position 3535, causing a translational frameshift with a predicted alternate stop codon (p.T1179Lfs*3). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration has been reported in the homozygous state in individuals with Bloom syndrome (Mitrofanova LB et al. Front Endocrinol (Lausanne), 2021 Aug;12:710947; Kasap B et al. Clin Dysmorphol, 2022 Jan;31:31-35). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

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