Submissions for variant NM_005585.5(SMAD6):c.533C>A (p.Ser178Ter)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002585070	SCV003489304	uncertain significance	Aortic valve disease 2	2022-10-10	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. This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser178*) 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.
Ambry Genetics	RCV004073389	SCV004953351	pathogenic	Inborn genetic diseases	2023-12-14	criteria provided, single submitter	clinical testing	The c.533C>A (p.S178*) alteration, located in exon 1 (coding exon 1) of the SMAD6 gene, consists of a C to A substitution at nucleotide position 533. This changes the amino acid from a serine (S) to a stop codon at amino acid position 178. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). Based on the available evidence, this alteration is classified as pathogenic.