ClinVar Miner

Submissions for variant NM_002880.3(RAF1):c.909A>C (p.Thr303=) (rs5746219)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen RASopathy Variant Curation Expert Panel RCV000233051 SCV000616487 likely benign Rasopathy 2017-04-18 reviewed by expert panel curation The filtering allele frequency of the c.909A>C (p.Thr303=) variant in the RAF1 gene is 0.0285% (27/66658) of European chromosomes by the Exome Aggregation Consortium, which is a high enough frequency to be classified as likely benign based on thresholds defined by the ClinGen RASopathy Expert Panel (BS1; PMID:29493581)
Illumina Clinical Services Laboratory,Illumina RCV000266115 SCV000440627 uncertain significance Noonan syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000318996 SCV000440628 uncertain significance Noonan syndrome with multiple lentigines 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000590617 SCV000698133 benign not provided 2016-11-21 criteria provided, single submitter clinical testing Variant summary: The RAF1 c.909A>C (p.Thr303Thr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 4/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 36/121308 control chromosomes at a frequency of 0.0002968, which is approximately 12 times the estimated maximal expected allele frequency of a pathogenic RAF1 variant (0.000025), suggesting this variant is very likely a benign polymorphism. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as Benign.
Invitae RCV000233051 SCV000287745 likely benign Rasopathy 2017-10-30 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000037710 SCV000061372 likely benign not specified 2015-06-09 criteria provided, single submitter clinical testing p.Thr303Thr in exon 9 of RAF1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 27/66658 European c hromosomes and 8/16512 South Asian chromosomes by the Exome Aggregation Consorti um (ExAC, http://exac.broadinstitute.org; dbSNP rs5746219).

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