Submissions for variant NM_005585.5(SMAD6):c.263del (p.Gly88fs)

dbSNP: rs1199495614

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568863	SCV003030076	uncertain significance	Aortic valve disease 2	2022-08-16	criteria provided, single submitter	clinical testing	In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. ClinVar contains an entry for this variant (Variation ID: 1174566). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Gly88Alafs*37) in the SMAD6 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in SMAD6 cause disease.
Mayo Clinic Laboratories, Mayo Clinic	RCV003481118	SCV004226892	likely pathogenic	not provided	2023-01-27	criteria provided, single submitter	clinical testing	PS4_supporting, PVS1
The Laboratory of Genetics and Metabolism, Hunan Children’s Hospital	RCV001799788	SCV001739411	pathogenic	Radioulnar synostosis	2020-06-20	no assertion criteria provided	research