Submissions for variant NM_000541.5(SAG):c.733G>A (p.Val245Met)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003064523	SCV003443794	uncertain significance	not provided	2022-08-23	criteria provided, single submitter	clinical testing	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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals affected with SAG-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change affects codon 245 of the SAG mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SAG protein. This variant also falls at the last nucleotide of exon 9, which is part of the consensus splice site for this exon.
Institute of Human Genetics, University of Leipzig Medical Center	RCV003224899	SCV003921004	uncertain significance	Retinitis pigmentosa 47	2023-03-15	criteria provided, single submitter	clinical testing	_x000D_ Criteria applied: PM2_SUP, PP3