Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002310920 | SCV000319494 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-02-04 | criteria provided, single submitter | clinical testing | The p.R1204Q variant (also known as c.3611G>A), located in coding exon 17 of the MYLK gene, results from a G to A substitution at nucleotide position 3611. The arginine at codon 1204 is replaced by glutamine, an amino acid with highly similar properties. This variant was identified in one individual with thoracic aortic aneurysm who also was heterozygous for an HCN4 variant (Arbustini E et al. J. Am. Coll. Cardiol., 2017 03;69:1210-1211). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on available evidence to date, the clinical significance of this alteration remains unclear. |
| Illumina Laboratory Services, |
RCV000793618 | SCV000440293 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV000793618 | SCV000932980 | uncertain significance | Aortic aneurysm, familial thoracic 7 | 2022-07-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1204 of the MYLK protein (p.Arg1204Gln). This variant is present in population databases (rs142421063, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with MYLK-related conditions. ClinVar contains an entry for this variant (Variation ID: 263940). 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 not expected to disrupt MYLK protein function. 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. |
| Fulgent Genetics, |
RCV002487145 | SCV002792605 | uncertain significance | Aortic aneurysm, familial thoracic 7; Megacystis-microcolon-intestinal hypoperistalsis syndrome 1 | 2021-09-07 | criteria provided, single submitter | clinical testing |