Submissions for variant NM_000057.4(BLM):c.1763del (p.Lys588fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002407621	SCV002716773	pathogenic	Hereditary cancer-predisposing syndrome	2021-04-12	criteria provided, single submitter	clinical testing	The c.1763delA pathogenic mutation, located in coding exon 6 of the BLM gene, results from a deletion of one nucleotide at nucleotide position 1763, causing a translational frameshift with a predicted alternate stop codon (p.K588Rfs*30). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003614161	SCV004407427	pathogenic	Bloom syndrome	2024-01-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Lys588Argfs*30) 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). 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: 1779622). For these reasons, this variant has been classified as Pathogenic.