Submissions for variant NM_005902.4(SMAD3):c.335C>T (p.Ala112Val)

dbSNP: rs387906854

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002313719	SCV000739666	uncertain significance	Familial thoracic aortic aneurysm and aortic dissection	2017-08-18	criteria provided, single submitter	clinical testing	The p.A112V variant (also known as c.335C>T), located in coding exon 2 of the SMAD3 gene, results from a C to T substitution at nucleotide position 335. The alanine at codon 112 is replaced by valine, an amino acid with similar properties, and is located in the MH1 domain. This alteration was detected in a family with a range of clinical features, including thoracic aortic aneurysm, bifid uvula, scoliosis, and/or early onset osteoarthritis, reported in mutation carriers (Regalado ES et al. Circ Res. 2011 Sep;109(6):680-6). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Institute of Human Genetics, University of Leipzig Medical Center	RCV000023247	SCV005368517	pathogenic	Aneurysm-osteoarthritis syndrome	2024-09-11	criteria provided, single submitter	clinical testing	Criteria applied: PS4_MOD,PM1,PM2,PM5,PP2,PP3
OMIM	RCV000023247	SCV000044538	pathogenic	Aneurysm-osteoarthritis syndrome	2011-09-02	no assertion criteria provided	literature only