Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000795564 | SCV000935031 | uncertain significance | Carnitine palmitoyl transferase 1A deficiency | 2022-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 499 of the CPT1A protein (p.Ala499Val). This variant is present in population databases (rs753866589, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with CPT1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 642158). 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 CPT1A protein function. 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. |
Ce |
RCV000994678 | SCV001148355 | uncertain significance | not provided | 2018-09-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003117584 | SCV003800894 | uncertain significance | not specified | 2023-01-11 | criteria provided, single submitter | clinical testing | Variant summary: CPT1A c.1496C>T (p.Ala499Val) results in a non-conservative amino acid change located in the Choline/carnitine acyltransferase domain (IPR039551) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 251476 control chromosomes (gnomAD). This frequency is not higher than predicted for a pathogenic variant in CPT1A causing Carnitine Palmitoyltransferase I Deficiency (7.6e-05 vs 0.0011), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1496C>T in individuals affected with Carnitine Palmitoyltransferase I Deficiency and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Natera, |
RCV000795564 | SCV001452928 | uncertain significance | Carnitine palmitoyl transferase 1A deficiency | 2020-03-17 | no assertion criteria provided | clinical testing |