Submissions for variant NM_133259.4(LRPPRC):c.1678A>T (p.Ile560Leu)

gnomAD frequency: 0.00058  dbSNP: rs144826521

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
CeGaT Center for Human Genetics Tuebingen	RCV000488138	SCV000575204	uncertain significance	not provided	2022-11-01	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000488138	SCV000706398	uncertain significance	not provided	2017-09-15	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764413	SCV000895470	uncertain significance	Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	2022-03-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001266183	SCV001444355	likely benign	Inborn genetic diseases	2021-03-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000488138	SCV003252663	uncertain significance	not provided	2022-08-20	criteria provided, single submitter	clinical testing	This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 560 of the LRPPRC protein (p.Ile560Leu). This variant is present in population databases (rs144826521, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with clinical features of Leigh syndrome (PMID: 34440436). ClinVar contains an entry for this variant (Variation ID: 214587). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Breakthrough Genomics, Breakthrough Genomics	RCV000488138	SCV005187649	uncertain significance	not provided		criteria provided, single submitter	not provided
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000488138	SCV001740596	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000488138	SCV001971418	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000764413	SCV002076563	uncertain significance	Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type	2020-01-16	no assertion criteria provided	clinical testing