ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4140T>G (p.Ser1380Arg)

gnomAD frequency: 0.00001  dbSNP: rs747834576
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000414956 SCV000795490 uncertain significance Bloom syndrome 2017-11-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000414956 SCV000933126 uncertain significance Bloom syndrome 2022-10-16 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1380 of the BLM protein (p.Ser1380Arg). This variant is present in population databases (rs747834576, gnomAD 0.003%). This missense change has been observed in individual(s) with multiple congenital anomalies (PMID: 27959697). ClinVar contains an entry for this variant (Variation ID: 374316). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function. 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.
Ambry Genetics RCV001021941 SCV001183619 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-12 criteria provided, single submitter clinical testing The p.S1380R variant (also known as c.4140T>G), located in coding exon 21 of the BLM gene, results from a T to G substitution at nucleotide position 4140. The serine at codon 1380 is replaced by arginine, an amino acid with dissimilar properties. This alteration was detected in a cohort of 7374 consecutive unrelated patients who had been referred to a clinical diagnostic laboratory for whole-exome sequencing (Posey JE et al. N Engl J Med, 2017 01;376:21-31). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV000414956 SCV000328795 uncertain significance Bloom syndrome 2016-05-01 no assertion criteria provided clinical testing Our laboratory reported two molecular diagnoses in GLI2 (NM_005270.4:c.3261dupC) and BLM (NM_000057.2:c.1544del; NM_000057.2:c.4140T>G; in trans) in an individual with failure to thrive, motor and speech delay, intellectual disability, abnormal movements, dysmorphic features, microcephaly, structural brain abnormalities, eye anomalies, congenital heart disease, kidney abnormalities, skeletal abnormalities, limb malformation, delayed bone age, genital anomalies, hypopituitarism, behavior problems, and holoprosencephaly.
Natera, Inc. RCV000414956 SCV002090663 uncertain significance Bloom syndrome 2018-09-27 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.