ClinVar Miner

Submissions for variant NM_000293.3(PHKB):c.781T>G (p.Ser261Ala)

gnomAD frequency: 0.00024  dbSNP: rs137946010
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001048947 SCV000397069 uncertain significance Glycogen storage disease IXb 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001048947 SCV001212977 uncertain significance Glycogen storage disease IXb 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 261 of the PHKB protein (p.Ser261Ala). This variant is present in population databases (rs137946010, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with PHKB-related conditions. ClinVar contains an entry for this variant (Variation ID: 319341). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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 RCV002522850 SCV003530768 uncertain significance Inborn genetic diseases 2021-08-12 criteria provided, single submitter clinical testing The c.781T>G (p.S261A) alteration is located in exon 9 (coding exon 9) of the PHKB gene. This alteration results from a T to G substitution at nucleotide position 781, causing the serine (S) at amino acid position 261 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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