Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostics Services |
RCV001090042 | SCV001237481 | likely pathogenic | CARASIL syndrome | 2020-03-21 | criteria provided, single submitter | clinical testing | The c.660C>G variant is not present in publicly available databases like 1000 Genomes, Exome Variant Server (EVS) and Exome Aggregation Consortium (ExAC). It is present in Genome Aggregation Database (gnomAD) and dbSNP at a very low frequency (MAF: 0.00001193), in heterozygous state. The variant is not present in our in-house exome database. The variant was not reported earlier to OMIM, ClinVar or Human Genome Mutation Database (HGMD), in any affected individuals. The variant is present in a highly conserved region and in-silico pathogenicity prediction programs like SIFT, PolyPhen-2, MutationTaster2, CADD etc. predicted this variant to be likely deleterious, however there are no documented functional studies to prove this. Since the phenotype is very specific, the variant has been classified as likely pathogenic. |
| Labcorp Genetics |
RCV002554804 | SCV003012335 | uncertain significance | not provided | 2024-05-31 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 220 of the HTRA1 protein (p.His220Gln). This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with HTRA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 870484). 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 expected to disrupt HTRA1 protein function with a positive predictive value of 80%. 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. |
| Institute of Human Genetics, |
RCV005245721 | SCV005900218 | uncertain significance | Cerebral arteriopathy, autosomal dominant, with subcortical infarcts and leukoencephalopathy, type 2 | 2025-03-04 | criteria provided, single submitter | clinical testing | Criteria applied: PM1,PM2_SUP,PP3 |