Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004409363 | SCV004891705 | uncertain significance | Inborn genetic diseases | 2023-10-10 | criteria provided, single submitter | clinical testing | The c.383A>G (p.K128R) alteration is located in exon 3 (coding exon 1) of the KLHL24 gene. This alteration results from a A to G substitution at nucleotide position 383, causing the lysine (K) at amino acid position 128 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV004787103 | SCV005398966 | uncertain significance | Cardiomyopathy, familial hypertrophic, 29, with polyglucosan bodies | 2024-10-08 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with cardiomyopathy with lethal arrhythmias (PMID: 30715372) and epidermolysis bullosa simplex, generalized, with scarring and hair loss (MIM#617294), respectively. Heterozygous start-loss variants resulting in reduced protein degradation have been reported in individuals with the epidermolysis bullosa phenotype, while biallelic loss of function variants are suggested to result in a cardiac condition (PMID: 30715372, PMID: 27889062). (I) 0108 - This gene is associated with both recessive and dominant disease. Start-loss variants with a gain of function affect are associated with epidermolysis bullosa simplex 6, and loss of function variants are associated with cardiomyopathy (PMID: 27889062; PMID: 30715372). (I) 0200 - Variant is predicted to result in a missense amino acid change from lysine to arginine. (I) 0252 - This variant is homozygous. (I) 0304 - Variant is present in gnomAD <0.01 for a recessive condition (v2 + v3: 2 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v3) (1 heterozygote, 0 homozygotes). (I) 0503 - Missense variant consistently predicted to be tolerated by multiple in silico tools or not conserved in placental mammals with a minor amino acid change. (SB) 0600 - Variant is located in the annotated BTB/POZ domain (DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |