ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.146T>C (p.Val49Ala)

dbSNP: rs1895601341
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001243845 SCV001417028 uncertain significance Bloom syndrome 2023-12-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 49 of the BLM protein (p.Val49Ala). 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: 968659). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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.
Genetic Services Laboratory, University of Chicago RCV001819945 SCV002066764 uncertain significance not specified 2021-01-07 criteria provided, single submitter clinical testing DNA sequence analysis of the BLM gene demonstrated a sequence change, c.146T>C, in exon 3 that results in an amino acid change, p.Val49Ala. This sequence change does not appear to have been previously described in individuals with BLM-related disorders and has also not been described in population databases (gnomAD, ExAC). The p.Val49Ala change affects a poorly conserved amino acid residue located in a domain of the BLM protein that is not known to be functional. The p.Val49Ala substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Due to these contrasting evidences and the lack of functional studies, the clinical significance of the p.Val49Ala change remains unknown at this time.
Ambry Genetics RCV002393642 SCV002702199 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-29 criteria provided, single submitter clinical testing The p.V49A variant (also known as c.146T>C), located in coding exon 2 of the BLM gene, results from a T to C substitution at nucleotide position 146. The valine at codon 49 is replaced by alanine, an amino acid with similar properties. This amino acid position is 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.
Natera, Inc. RCV001243845 SCV002089893 uncertain significance Bloom syndrome 2020-05-29 no assertion criteria provided clinical testing

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