ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.1A>C (p.Met1Leu) (rs730880097)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Integrated Genetics/Laboratory Corporation of America RCV000587707 SCV000695475 likely pathogenic Marfan Syndrome/Loeys-Dietz Syndrome/Familial Thoracic Aortic Aneurysms and Dissections 2016-02-12 criteria provided, single submitter clinical testing Variant summary: FBN1 c.1A>C variant affects a conserved nucleotide in the initiation codon, resulting in amino acid change from Met to Leu. 3/4 in-silico tools predict this variant to be benign (SNPs&GO not captured due to low reliability index). However, this variant disrupts the initiation codon of FBN1, thus it is expected to result in no protein product or a dramatically altered product. These predictions have not been tested via in vivo/vitro functional studies. This variant was not found in 104502 control chromosomes, and has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical laboratories. However, a similar variant, c.1A>T, that results in the same amino acid change (Met1Leu) has been cited in at least 2 MFS patients from independent families (PMID: 19159394; PMID: 19012347) and is considered pathogenic in HGMD. Taken together, this is probably a disease variant and was classified as likely pathogenic.
Ambry Genetics RCV000617649 SCV000738852 pathogenic Cardiovascular phenotype 2016-11-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Rarity in general population databases (dbsnp, esp, 1000 genomes),Well-characterized mutation at same position
Center for Medical Genetics Ghent,University of Ghent RCV000663511 SCV000786817 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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