Submissions for variant NM_001330311.2(DVL1):c.1054G>C (p.Ala352Pro)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003083060	SCV003488396	uncertain significance	not provided	2023-05-13	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 352 of the DVL1 protein (p.Ala352Pro). This variant also falls at the last nucleotide of exon 10, which is part of the consensus splice site for this exon. 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 variant has not been reported in the literature in individuals affected with DVL1-related conditions. ClinVar contains an entry for this variant (Variation ID: 2172481). 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.