Submissions for variant NM_017837.4(PIGV):c.348G>A (p.Leu116=)

gnomAD frequency: 0.00096  dbSNP: rs148662665

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000376742	SCV000357199	uncertain significance	Hyperphosphatasia with intellectual disability syndrome 1	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000455608	SCV000540032	likely benign	not specified	2016-03-29	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Silent variant (on both ref transcripts) on its own, but it is in cis with c.349A>G variant in this patient (please see IGV screenshot in the case folder). These two variants result in c.348_349delinsAG. (p.Ile117Val).
CeGaT Center for Human Genetics Tuebingen	RCV000512822	SCV000608469	likely benign	not provided	2023-03-01	criteria provided, single submitter	clinical testing	PIGV: BP4, BP7
Labcorp Genetics (formerly Invitae), Labcorp	RCV000512822	SCV001110037	benign	not provided	2019-12-31	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000376742	SCV003920322	likely benign	Hyperphosphatasia with intellectual disability syndrome 1	2022-07-12	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature but is present in the Genome Aggregation Database (Highest reported MAF 0.1% (105/68046) (https://gnomad.broadinstitute.org/variant/1-26794382-G-A?dataset=gnomad_r3). This variant is present in ClinVar, with multiple labs classifying this variant as Likely Benign or Benign (Variation ID:297115). Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. Of note, this variant is a silent variant and does not change the amino acid, reducing the probability that this variant is disease causing. In summary, data on this variant suggests that this variant does not cause disease but requires further evidence. Therefore, this variant is classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004537667	SCV004728806	likely benign	PIGV-related disorder	2022-09-09	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).