Submissions for variant NM_194318.4(B3GLCT):c.181G>A (p.Val61Ile)

gnomAD frequency: 0.00021  dbSNP: rs375667011

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000593789	SCV000702636	uncertain significance	not provided	2016-11-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001113160	SCV001270910	uncertain significance	Peters plus syndrome	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.
Invitae	RCV001113160	SCV003241904	uncertain significance	Peters plus syndrome	2022-06-28	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 497890). 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with B3GLCT-related conditions. This variant is present in population databases (rs375667011, gnomAD 0.06%). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 61 of the B3GLCT protein (p.Val61Ile).
Ambry Genetics	RCV004024723	SCV004913719	uncertain significance	Inborn genetic diseases	2022-06-09	criteria provided, single submitter	clinical testing	The c.181G>A (p.V61I) alteration is located in exon 4 (coding exon 4) of the B3GLCT gene. This alteration results from a G to A substitution at nucleotide position 181, causing the valine (V) at amino acid position 61 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.