Submissions for variant NM_001330311.2(DVL1):c.1594del (p.Trp532fs)

dbSNP: rs797044835

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
3billion	RCV000195250	SCV002012136	pathogenic	Autosomal dominant Robinow syndrome 2	2021-10-02	criteria provided, single submitter	clinical testing	Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). It is not observed in the gnomAD v2.1.1 dataset (PM2). The variant was observed as assumed (i.e. paternity and maternity not confirmed) de novoo (3billion dataset, PM6). The variant has been reported as pathogenic/likely pathogenic without evidence for the classification (ClinVar ID: VCV000504195.6). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline.
GeneDx	RCV003223617	SCV003919668	pathogenic	not provided	2023-04-20	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation, as the last 164 amino acids are replaced with 141 different amino acids, and other loss-of-function variants have been reported downstream in HGMD; Not observed at significant frequency in large population cohorts (gnomAD); Published functional studies suggest a damaging gain of function effect (Bunn et al., 2015); This variant is associated with the following publications: (PMID: 30266093, 25817016, 25817014, 32888393, 33237614, 35047859)
Labcorp Genetics (formerly Invitae), Labcorp	RCV003223617	SCV005833820	pathogenic	not provided	2025-01-08	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp507Glyfs*142) in the DVL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 164 amino acid(s) of the DVL1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Robinow syndrome (PMID: 25817014, 25817016, 35047859). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 208045). For these reasons, this variant has been classified as Pathogenic.
OMIM	RCV000195250	SCV000222663	pathogenic	Autosomal dominant Robinow syndrome 2	2015-04-02	no assertion criteria provided	literature only
GeneReviews	RCV000195250	SCV000243849	not provided	Autosomal dominant Robinow syndrome 2		no assertion provided	literature only
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine	RCV000195250	SCV000256688	pathogenic	Autosomal dominant Robinow syndrome 2	2020-09-30	no assertion criteria provided	research