ClinVar Miner

Submissions for variant NM_001876.4(CPT1A):c.1436C>T (p.Pro479Leu) (rs80356779)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000079911 SCV000225586 pathogenic not provided 2014-06-19 criteria provided, single submitter clinical testing
GeneDx RCV000079911 SCV000321521 pathogenic not provided 2018-10-10 criteria provided, single submitter clinical testing The P479L variant in the CPT1A gene is a common variant in individuals with CPT1A deficiency from the Inuit and Alaska Native populations (Bennett and Santani, 2016). Expression of P479L in COS cells found that it is associated with reduced CPT1A enzyme activity compared to wild type (Brown et al., 2001). The high frequency of P479L homozygotes in certain populations indicates that under normal circumstances individuals with this genotype are rarely symptomatic. However, children homozygous for P479L have shown abnormal metabolic response to prolonged fasting and may have an increased risk for infant mortality (Collins et al., 2010; Gillingham et al., 2011; Sinclair et al., 2012; Gessner et al., 2016). Therefore, we interpret P479L to be a pathogenic variant.
GeneReviews RCV000055857 SCV000086856 pathologic Carnitine palmitoyltransferase I deficiency 2013-03-07 no assertion criteria provided curation Converted during submission to Pathogenic.
Invitae RCV000551382 SCV000638094 pathogenic Carnitine palmitoyl transferase 1 deficiency 2018-03-29 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 479 of the CPT1A protein (p.Pro479Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs80356779, ExAC 0.009%). This is a prevalent CPT1 deficiency variant in certain Inuit populations. Family analysis showed that this variant co-segregates with disease and in most affected individuals this variant is in the homozygous state (PMID: 20696606, 20301700, 19217814). ClinVar contains an entry for this variant (Variation ID: 65644) Experimental studies have shown that this variant is associated with high residual CPT1A enzyme activity (PMID: 11441142). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000714476 SCV000845174 benign CARNITINE PALMITOYLTRANSFERASE IA POLYMORPHISM 2001-07-01 no assertion criteria provided literature only
OMIM RCV000714477 SCV000845175 pathogenic CPT1A ARCTIC VARIANT 2001-07-01 no assertion criteria provided literature only

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