Submissions for variant NM_201525.4(ADGRG1):c.944_945dup (p.Val316fs)

dbSNP: rs797045602

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000193721	SCV000247499	pathogenic	Bilateral frontoparietal polymicrogyria	2013-02-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000482949	SCV000569198	pathogenic	not provided	2016-01-20	criteria provided, single submitter	clinical testing	The c.944_945dupTT pathogenic variant in the GPR56 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.944_945dupTT variant causes a frameshift starting with codon Valine 316, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 8 of the new reading frame, denoted p.Val316LeufsX8. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.944_945dupTT variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.944_945dupTT as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000482949	SCV001583482	pathogenic	not provided	2020-08-27	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in ADGRG1 are known to be pathogenic (PMID: 15044805, 20929962). This variant has not been reported in the literature in individuals with ADGRG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 211096). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val316Leufs*8) in the ADGRG1 gene. It is expected to result in an absent or disrupted protein product.