Submissions for variant NM_001352514.2(HLCS):c.865G>A (p.Val289Ile)

gnomAD frequency: 0.00087  dbSNP: rs149291867

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000352340	SCV000436054	uncertain significance	Holocarboxylase synthetase deficiency	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.
GeneDx	RCV001705508	SCV000513239	likely benign	not provided	2018-04-26	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000438140	SCV000539303	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: See above.
Invitae	RCV000352340	SCV000756240	benign	Holocarboxylase synthetase deficiency	2024-01-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000352340	SCV001716347	uncertain significance	Holocarboxylase synthetase deficiency	2021-05-18	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002523179	SCV003695049	likely benign	Inborn genetic diseases	2021-04-03	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV001705508	SCV004153628	benign	not provided	2022-08-01	criteria provided, single submitter	clinical testing	HLCS: BS1, BS2
PreventionGenetics, part of Exact Sciences	RCV003910323	SCV004736826	benign	HLCS-related condition	2019-05-24	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).