Submissions for variant NM_000138.5(FBN1):c.62C>T (p.Thr21Met)

gnomAD frequency: 0.00002  dbSNP: rs1489806847

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001180957	SCV001346010	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2023-02-02	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with methionine at codon 21 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/282722 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194175	SCV001363509	uncertain significance	not specified	2019-03-04	criteria provided, single submitter	clinical testing	Variant summary: FBN1 c.62C>T (p.Thr21Met) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 277066 control chromosomes, predominantly at a frequency of 0.00026 within the Latino subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.62C>T in individuals affected with Marfan Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001876009	SCV002220121	likely benign	Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection	2023-12-25	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004006704	SCV004823162	uncertain significance	Marfan syndrome	2023-03-07	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with methionine at codon 21 of the FBN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 9/282722 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.