Submissions for variant NM_001330311.2(DVL1):c.1731del (p.Ser578fs)

dbSNP: rs1553172962

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000598780	SCV000710505	likely pathogenic	not provided	2020-07-29	criteria provided, single submitter	clinical testing	Not observed in large population cohorts (Lek et al., 2016); Frameshift variant predicted to result in protein truncation as the last 118 amino acids are replaced with 95 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000598780	SCV003238791	uncertain significance	not provided	2022-10-04	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with DVL1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ser553Profs*96) in the DVL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 118 amino acid(s) of the DVL1 protein. ClinVar contains an entry for this variant (Variation ID: 504195). 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.
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV001353070	SCV001438004	pathogenic	Autosomal dominant Robinow syndrome 2	2020-07-14	no assertion criteria provided	research