Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001316975 | SCV001507617 | uncertain significance | Hereditary sensory and autonomic neuropathy type 1 | 2020-07-26 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with hereditary sensory neuropathy (PMID: 19555464). ClinVar contains an entry for this variant (Variation ID: 637417). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys133 amino acid residue in SPTLC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11242106, 11242114, 16364956, 18018475, 22302274, 26681808, 15546589). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This sequence change replaces cysteine with arginine at codon 133 of the SPTLC1 protein (p.Cys133Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. |
| Mayo Clinic Laboratories, |
RCV001508628 | SCV001714901 | uncertain significance | not provided | 2019-08-17 | criteria provided, single submitter | clinical testing | |
| Inherited Neuropathy Consortium | RCV000789582 | SCV000928938 | uncertain significance | Charcot-Marie-Tooth disease | no assertion criteria provided | literature only |