ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3651A>T (p.Lys1217Asn) (rs587779887)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115310 SCV000149219 uncertain significance not provided 2013-10-14 criteria provided, single submitter clinical testing This variant is denoted BLM c.3651A>T at the cDNA level, p.Lys1217Asn (K1217N) at the protein level, and results in the change of a Lysine to an Asparagine (AAA>AAT) in exon 19. This variant has not, to our knowledge, been published in the literature as either a mutation or a benign polymorphism, nor has it been observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Variant Server, indicating it is not a common benign variant in these populations. This variant is a non-conservative substitution of a positive polar amino acid for a neutral polar one, altering a position that is well conserved throughout evolution and is located in the Helicase and Rnase-D C-terminal domain. In silico analyses are inconsistent with regard to the effect this variant may have on protein structure and function. Based on the currently available information, we cannot assess whether this variant is benign or pathogenic, and therefore consider to be of unknown significance.The variant is found in HEREDICANCER panel(s).
Invitae RCV000700971 SCV000829750 uncertain significance Bloom syndrome 2018-12-08 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 1217 of the BLM protein (p.Lys1217Asn). The lysine residue is moderately conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs587779887, ExAC 0.01%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 127502). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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.

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