ClinVar Miner

Submissions for variant NM_007194.4(CHEK2):c.937G>A (p.Val313Met) (rs752302543)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000466569 SCV000550502 uncertain significance Familial cancer of breast 2020-03-17 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 313 of the CHEK2 protein (p.Val313Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs752302543, ExAC 0.04%). This variant has been observed in individuals affected with breast and/or ovarian cancer (PMID: 29470806). ClinVar contains an entry for this variant (Variation ID: 410041). 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: Deleterious; PolyPhen-2: Probably 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.
Color Health, Inc RCV000582321 SCV000689749 uncertain significance Hereditary cancer-predisposing syndrome 2020-12-22 criteria provided, single submitter clinical testing This missense variant replaces valine with methionine at codon 313 of the CHEK2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in two Indian individuals affected with breast and/or ovarian cancer (PMID: 29470806). This variant has been identified in 15/251446 chromosomes (15/30612 South Asian chromosomes) in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Counsyl RCV000466569 SCV000785787 uncertain significance Familial cancer of breast 2017-11-30 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000765619 SCV000896944 uncertain significance Familial cancer of breast; Li-Fraumeni syndrome 2; Bone osteosarcoma; Malignant tumor of prostate 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000582321 SCV001180558 uncertain significance Hereditary cancer-predisposing syndrome 2019-01-29 criteria provided, single submitter clinical testing The p.V313M variant (also known as c.937G>A), located in coding exon 8 of the CHEK2 gene, results from a G to A substitution at nucleotide position 937. The valine at codon 313 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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