Submissions for variant NM_194318.4(B3GLCT):c.56T>C (p.Leu19Pro)

gnomAD frequency: 0.00018  dbSNP: rs999173078

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000696889	SCV000825470	uncertain significance	Peters plus syndrome	2020-01-27	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. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with B3GLCT-related disease. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This sequence change replaces leucine with proline at codon 19 of the B3GLCT protein (p.Leu19Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline.
Illumina Laboratory Services, Illumina	RCV000696889	SCV001268671	uncertain significance	Peters plus syndrome	2018-01-12	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.
Ambry Genetics	RCV003163208	SCV003874947	uncertain significance	Inborn genetic diseases	2023-01-24	criteria provided, single submitter	clinical testing	The c.56T>C (p.L19P) alteration is located in exon 1 (coding exon 1) of the B3GLCT gene. This alteration results from a T to C substitution at nucleotide position 56, causing the leucine (L) at amino acid position 19 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.