Submissions for variant NM_000098.3(CPT2):c.1897G>T (p.Ala633Ser)

gnomAD frequency: 0.00001  dbSNP: rs141903761

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000811230	SCV000951486	uncertain significance	Carnitine palmitoyltransferase II deficiency	2023-12-10	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 633 of the CPT2 protein (p.Ala633Ser). This variant is present in population databases (rs141903761, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with CPT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 655118). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CPT2 protein function with a negative predictive value of 80%. 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.
Illumina Laboratory Services, Illumina	RCV000811230	SCV001254944	uncertain significance	Carnitine palmitoyltransferase II 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.
Genome-Nilou Lab	RCV003456148	SCV004178350	uncertain significance	Encephalopathy, acute, infection-induced, susceptibility to, 4	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453695	SCV004178351	uncertain significance	Carnitine palmitoyl transferase II deficiency, severe infantile form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453697	SCV004178352	uncertain significance	Carnitine palmitoyl transferase II deficiency, neonatal form	2023-04-11	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003453696	SCV004178354	uncertain significance	Carnitine palmitoyl transferase II deficiency, myopathic form	2023-04-11	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000811230	SCV001456154	uncertain significance	Carnitine palmitoyltransferase II deficiency	2020-01-24	no assertion criteria provided	clinical testing