Submissions for variant NM_022114.4(PRDM16):c.2449G>A (p.Gly817Ser)

gnomAD frequency: 0.00057  dbSNP: rs375308440

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088110	SCV000290646	likely benign	Left ventricular noncompaction 8	2025-01-27	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000611940	SCV000711463	uncertain significance	not specified	2016-08-14	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gly817Ser var iant in PRDM16 has not been previously reported in individuals with cardiomyopat hy, but has been identified in 0.2% (6/2466) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs375308440 ). Computational prediction tools and conservation analysis suggest that the p.G ly817Ser variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, while the clinical significanc e of the p.Gly817Ser variant is uncertain, its frequency suggests that it is mor e likely to be benign.
GeneDx	RCV000828659	SCV000970356	likely benign	not provided	2021-01-04	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30847666)
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV001088110	SCV003920345	uncertain significance	Left ventricular noncompaction 8		criteria provided, single submitter	clinical testing	PRDM16 NM_022114.3 exon 9 p.Gly817Ser (c.2449G>A): This variant has not been reported in the literature but is present in 0.2% (41/18334) of African alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/1-3329210-G-A). This variant is present in ClinVar (Variation ID:241425). Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
PreventionGenetics, part of Exact Sciences	RCV003919978	SCV004732552	likely benign	PRDM16-related disorder	2022-03-25	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).