ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1949C>T (p.Pro650Leu)

dbSNP: rs2151160613
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001955885 SCV002221150 uncertain significance Bloom syndrome 2021-07-28 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 650 of the BLM protein (p.Pro650Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with BLM-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004699576 SCV005204347 uncertain significance not specified 2024-06-12 criteria provided, single submitter clinical testing Variant summary: BLM c.1949C>T (p.Pro650Leu) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 250998 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1949C>T has been reported in the literature in a heterozygous individual affected with premature ovarian insufciency (Ke_2023). To our knowledge, no occurrence of c.1949C>T in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. The following publication have been ascertained in the context of this evaluation (PMID: 36732629). ClinVar contains an entry for this variant (Variation ID: 1444369). Based on the evidence outlined above, the variant was classified as uncertain significance.

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