ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3827C>T (p.Ala1276Val)

gnomAD frequency: 0.00001  dbSNP: rs760554566
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics RCV000224500 SCV000281267 uncertain significance not provided 2015-09-29 criteria provided, single submitter clinical testing Converted during submission to Uncertain significance.
Ambry Genetics RCV000570830 SCV000672968 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-21 criteria provided, single submitter clinical testing The c.3827C>T (p.A1276V) alteration is located in exon 20 (coding exon 19) of the BLM gene. This alteration results from a C to T substitution at nucleotide position 3827, causing the alanine (A) at amino acid position 1276 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001232070 SCV001404615 uncertain significance Bloom syndrome 2024-09-01 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1276 of the BLM protein (p.Ala1276Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). 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: 235580). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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 RCV000224500 SCV005441416 uncertain significance not provided 2024-06-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Natera, Inc. RCV001232070 SCV001456905 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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