Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000250770 | SCV000318756 | uncertain significance | Cardiovascular phenotype | 2013-06-10 | criteria provided, single submitter | clinical testing | There is insufficient or conflicting evidence for classification of this alteration. |
| Stanford Center for Inherited Cardiovascular Disease, |
RCV000223813 | SCV000280285 | uncertain significance | not specified | 2011-08-05 | no assertion criteria provided | clinical testing | Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease. p.Phe295Ser Based on the data reviewed below we consider this variant a variant of uncertain significance. This variant is novel. The Phe295Ser variant is located in exon 9 of the MYBPC3 gene. The phenylalanine is replaced by serine, an amino acid with dissimilar properties (phenylalanine is non-polar, neutral; serine is polar, neutral). In silico analysis with PolyPhen-2 predicts the variant to be probably damaging. The phenyalanine at codon 295 is highly conserved across species, as are neighboring amino acids. In total the variant has not been seen in ~6,500 laboratory controls, published controls and individuals from publicly available population datasets. There is no variation at codon 295 listed in the NHLBI Exome Sequencing Project dataset, which currently includes variant calls on ~6,500 Caucasian and African American individuals (as of 8/1/13). There is also no variation at this codon listed in dbSNP or 1000 genomes (as of 8/1/13). Ambry genetics did not include internal control data. |