ClinVar Miner

Submissions for variant NM_001042492.3(NF1):c.2248A>G (p.Thr750Ala)

gnomAD frequency: 0.00001  dbSNP: rs748064845
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165422 SCV000216151 uncertain significance Hereditary cancer-predisposing syndrome 2015-05-21 criteria provided, single submitter clinical testing The p.T750A variant (also known as c.2248A>G), located in coding exon 18 of the NF1 gene, results from an A to G substitution at nucleotide position 2248. The threonine at codon 750 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 0.004% (greater than 55000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be possibly damaging and tolerated by PolyPhen and SIFT in silico analyses, respectively. Since supporting evidence is limited at this time, the clinical significance of p.T750A remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000465924 SCV000541994 likely benign Neurofibromatosis, type 1 2024-12-09 criteria provided, single submitter clinical testing
GeneDx RCV000681212 SCV000808672 uncertain significance not provided 2020-09-08 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with breast cancer (Yehia 2018); This variant is associated with the following publications: (PMID: 29684080)
Mendelics RCV000465924 SCV000839137 uncertain significance Neurofibromatosis, type 1 2018-07-02 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000465924 SCV002562014 uncertain significance Neurofibromatosis, type 1 2022-03-15 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV000681212 SCV003917910 likely benign not provided 2023-03-01 criteria provided, single submitter clinical testing NF1: BP1
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479036 SCV004223786 uncertain significance not specified 2023-11-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV004558374 SCV005047609 uncertain significance Hereditary cancer-predisposing syndrome; Cardiovascular phenotype 2021-07-14 criteria provided, single submitter clinical testing The c.2248A>G (p.T750A) alteration is located in exon 18 (coding exon 18) of the NF1 gene. This alteration results from a A to G substitution at nucleotide position 2248, causing the threonine (T) at amino acid position 750 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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