Submissions for variant NM_032119.4(ADGRV1):c.5967dup (p.Val1990fs)

dbSNP: rs778288846

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001009156	SCV001168972	likely pathogenic	not provided	2018-12-18	criteria provided, single submitter	clinical testing	The c.5967dupA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). It causes a frameshift starting with codon Valine 1990, changes this amino acid to a Serine residue and creates a premature Stop codon at position 2 of the new reading frame, denoted p.Val1990SerfsX2. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. We consider this variant to be likely pathogenic.
Invitae	RCV001009156	SCV001199946	pathogenic	not provided	2023-11-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val1990Serfs*2) in the ADGRV1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADGRV1 are known to be pathogenic (PMID: 19357117, 22135276, 22147658, 26226137, 30718709, 31047384, 32467589). This variant is present in population databases (rs778288846, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with clinical features of Usher syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 817925). For these reasons, this variant has been classified as Pathogenic.