ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1064C>G (p.Pro355Arg)

dbSNP: rs1022898915
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000535187 SCV000623220 uncertain significance Bloom syndrome 2024-04-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 355 of the BLM protein (p.Pro355Arg). 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: 454061). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV001009800 SCV001169914 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-13 criteria provided, single submitter clinical testing The p.P355R variant (also known as c.1064C>G), located in coding exon 4 of the BLM gene, results from a C to G substitution at nucleotide position 1064. The proline at codon 355 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly 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.
Genetic Services Laboratory, University of Chicago RCV001821467 SCV002068073 uncertain significance not specified 2020-04-16 criteria provided, single submitter clinical testing DNA sequence analysis of the BLM gene demonstrated a sequence change, c.1064C>G, in exon 5 that results in an amino acid change, p.Pro355Arg. This sequence change does not appear to have been previously described in patients with BLM-related disorders and has also not been described in the population databases (ExAC and gnomAD). The p.Pro355Arg 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.Pro355Arg 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.Pro355Arg change remains unknown at this time.
Natera, Inc. RCV000535187 SCV001466156 uncertain significance Bloom syndrome 2020-09-04 no assertion criteria provided clinical testing

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