Submissions for variant NM_014324.6(AMACR):c.437C>T (p.Pro146Leu)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV002679205	SCV003725023	uncertain significance	Inborn genetic diseases	2021-03-31	criteria provided, single submitter	clinical testing	The c.437C>T (p.P146L) alteration is located in exon 3 (coding exon 3) of the AMACR gene. This alteration results from a C to T substitution at nucleotide position 437, causing the proline (P) at amino acid position 146 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Invitae	RCV003108218	SCV003792567	uncertain significance	Alpha-methylacyl-CoA racemase deficiency	2022-05-10	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 146 of the AMACR protein (p.Pro146Leu). This variant is present in population databases (rs757917164, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AMACR-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. 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.
CeGaT Center for Human Genetics Tuebingen	RCV003434673	SCV004160823	uncertain significance	not provided	2023-09-01	criteria provided, single submitter	clinical testing	AMACR: PM2, PM3