Submissions for variant NM_006258.4(PRKG1):c.700G>A (p.Val234Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002999531	SCV003297863	uncertain significance	Aortic aneurysm, familial thoracic 8	2025-01-01	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 234 of the PRKG1 protein (p.Val234Ile). This variant is present in population databases (rs368571406, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PRKG1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2082951). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences	RCV003427542	SCV004117600	uncertain significance	PRKG1-related disorder	2023-07-18	criteria provided, single submitter	clinical testing	The PRKG1 c.700G>A variant is predicted to result in the amino acid substitution p.Val234Ile. This variant has been reported as de novo in an individual from a cohort of children with neurodevelopmental disorders along with other do novo synonymous variants in ELP4 and DMBT1 genes (reported with genomic position 53667268 in Table S2, Turner et al. 2019. PubMed ID: 31785789). This variant is reported in 0.012% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/10-53667268-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.