Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000973228 | SCV001120969 | likely benign | not provided | 2018-07-04 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV004029970 | SCV004053646 | uncertain significance | not specified | 2023-09-13 | criteria provided, single submitter | clinical testing | The c.3100G>A (p.V1034M) alteration is located in exon 26 (coding exon 25) of the ANAPC1 gene. This alteration results from a G to A substitution at nucleotide position 3100, causing the valine (V) at amino acid position 1034 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Breakthrough Genomics, |
RCV000973228 | SCV005262691 | likely benign | not provided | criteria provided, single submitter | not provided | ||
Department of Pathology and Laboratory Medicine, |
RCV001355438 | SCV001550324 | uncertain significance | Rothmund-Thomson syndrome type 1 | no assertion criteria provided | clinical testing | The ANAPC1 p.V1034M variant was not identified in the literature but was identified in dbSNP (ID: rs548028803) and ClinVar (classified as likely benign by Invitae). The variant was identified in control databases in 240 of 147822 chromosomes (1 homozygous) at a frequency of 0.001624, and was observed at the highest frequency in the European (non-Finnish) population in 165 of 59988 chromosomes (freq: 0.002751) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.V1034 residue is conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance. |