ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.4942A>G (p.Thr1648Ala)

gnomAD frequency: 0.00003  dbSNP: rs770558820
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000219524 SCV000275998 uncertain significance Hereditary cancer-predisposing syndrome 2016-03-04 criteria provided, single submitter clinical testing The p.T1648A variant (also known as c.4942A>G), located in coding exon 37 of the NF1 gene, results from an A to G substitution at nucleotide position 4942. The threonine at codon 1648 is replaced by alanine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 110000 alleles tested) in our clinical cohort.This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence for this variant is limited at this time, the clinical significance ofp.T1648A remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000469644 SCV000542175 likely benign Neurofibromatosis, type 1 2025-01-19 criteria provided, single submitter clinical testing
Cancer Genomics Group, Japanese Foundation For Cancer Research RCV001030577 SCV001193667 uncertain significance Hereditary breast ovarian cancer syndrome 2019-05-01 criteria provided, single submitter research
GeneDx RCV001567513 SCV001791216 likely benign not provided 2019-09-19 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 23913538)
Sema4, Sema4 RCV000219524 SCV002527596 uncertain significance Hereditary cancer-predisposing syndrome 2021-10-20 criteria provided, single submitter curation
Ambry Genetics RCV002338691 SCV002634963 likely benign Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2020-06-17 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.

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