ClinVar Miner

Submissions for variant NM_000268.4(NF2):c.1774T>C (p.Phe592Leu)

gnomAD frequency: 0.00003  dbSNP: rs764972504
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000468324 SCV000553682 uncertain significance Neurofibromatosis, type 2 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 592 of the NF2 protein (p.Phe592Leu). This variant is present in population databases (rs764972504, gnomAD 0.02%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with NF2-related conditions. ClinVar contains an entry for this variant (Variation ID: 412213). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt NF2 protein function with a positive predictive value of 80%. 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.
CeGaT Center for Human Genetics Tuebingen RCV000997902 SCV001153665 uncertain significance not provided 2022-11-01 criteria provided, single submitter clinical testing NF2: PP3
Ambry Genetics RCV001013097 SCV001173637 benign Hereditary cancer-predisposing syndrome 2021-06-16 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000468324 SCV001306003 likely benign Neurofibromatosis, type 2 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Baylor Genetics RCV000468324 SCV002030263 uncertain significance Neurofibromatosis, type 2 2021-03-04 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Genome-Nilou Lab RCV000468324 SCV002045417 likely benign Neurofibromatosis, type 2 2021-11-07 criteria provided, single submitter clinical testing
Center of Medical Genetics and Primary Health Care RCV001269377 SCV001448713 uncertain significance Malignant tumor of breast no assertion criteria provided clinical testing

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