ClinVar Miner

Submissions for variant NM_000298.6(PKLR):c.829G>A (p.Glu277Lys) (rs147689373)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000946502 SCV001092644 likely benign not provided 2018-12-20 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001001692 SCV001159263 uncertain significance not specified 2019-03-06 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001097711 SCV001254014 uncertain significance Pyruvate kinase deficiency of red cells 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Mayo Clinic Laboratories, Mayo Clinic RCV000946502 SCV001715316 uncertain significance not provided 2021-03-11 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000946502 SCV001551809 uncertain significance not provided no assertion criteria provided clinical testing The PKLR p.Glu246Lys variant was not identified in the literature nor was it identified in ClinVar, Cosmic, or LOVD 3.0. The variant was identified in dbSNP (ID: rs147689373) and in control databases in 242 of 282216 chromosomes (2 homozygous) at a frequency of 0.000857 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 215 of 24902 chromosomes (freq: 0.008634), Latino in 21 of 35410 chromosomes (freq: 0.0005931), Other in 2 of 7200 chromosomes (freq: 0.0002778), South Asian in 3 of 30598 chromosomes (freq: 0.00009805) and European (non-Finnish) in 1 of 128714 chromosomes (freq: 0.000007769), while the variant was not observed in the Ashkenazi Jewish, European (Finnish) or East Asian populations. The p.Glu246 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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