Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000761812 | SCV000223403 | uncertain significance | not provided | 2018-12-10 | criteria provided, single submitter | clinical testing | p.Ala68Thr (GCT>ACT): c.202 G>A in exon 2 of the CACNA1C gene (NM_000719.6). The A68T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A68T variant was not observed in approximately 6,300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The A68T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position that is not conserved across species. In silico analysis predicts this variant likely does not alter the protein structure/function. No missense mutations in nearby residues have been reported in association with LQTS, indicating this region of the protein may be tolerant of change. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in LQT panel(s). |
Illumina Laboratory Services, |
RCV000357698 | SCV000377588 | uncertain significance | Timothy syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000262517 | SCV000377589 | uncertain significance | Brugada syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Center For Human Genetics And Laboratory Diagnostics, |
RCV000357698 | SCV000805139 | uncertain significance | Timothy syndrome | 2018-01-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000761812 | SCV000892013 | uncertain significance | not provided | 2018-05-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000781192 | SCV000919075 | likely benign | not specified | 2017-11-06 | criteria provided, single submitter | clinical testing | Variant summary: The CACNA1C c.202G>A (p.Ala68Thr) variant involves the alteration of a conserved nucleotide and 2/3 in silico tools predict a benign outcome for this variant (SNPsandGO and MutationTaster not captured here due to low reliability index and p-value, respectively). This variant was found in 41/261782 control chromosomes at a frequency of 0.0001566, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.000309 (37/119594). This frequency is about 31 times the estimated maximal expected allele frequency of a pathogenic CACNA1C variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. This variant has been reported in multiple affected individuals without strong evidence for casualty. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as uncertain significance, without evidence for independent evaluation. Taken together, this variant is classified as likely benign. |
Invitae | RCV000794589 | SCV000934007 | likely benign | Long QT syndrome | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Centre for Mendelian Genomics, |
RCV000357698 | SCV001367871 | uncertain significance | Timothy syndrome | 2016-01-01 | criteria provided, single submitter | clinical testing | This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PP3,PP4. |
Ambry Genetics | RCV002415722 | SCV002721833 | benign | Cardiovascular phenotype | 2021-12-13 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |