Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000672781 | SCV000797921 | uncertain significance | Deficiency of hydroxymethylglutaryl-CoA lyase | 2018-02-14 | criteria provided, single submitter | clinical testing | |
Neuberg Centre For Genomic Medicine, |
RCV000672781 | SCV004048325 | likely pathogenic | Deficiency of hydroxymethylglutaryl-CoA lyase | criteria provided, single submitter | clinical testing | The HMGCL (c.825C>G) (p.Asn275Lys) variant has been reported as one of the double heterozygous (c.109G>T (p.Glu37*) variant in an individual affected with HMG-CoA lyase deficiency (Puisac B et. al., 2013). The p.Asn275Lys variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. It has been submitted to ClinVar with as Variant of Uncertain Significance (VUS) but no details are available for independent assessment. The amino acid Asn at position 275 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. The variant is predicted to be probably damaging by PolyPhen 2 and deleterious by SIFT. For these reasons, this variant has been classified as Likely Pathogenic. In the absence of another reportable variant the molecular diagnosis is not confirmed. |