rs1060500727
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_002474.3(MYH11):āc.4517A>Gā(p.Asn1506Ser) variant causes a missense change. The variant allele was found at a frequency of 0.00000342 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N1506K) has been classified as Uncertain significance.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.4517A>G | p.Asn1506Ser | missense_variant | 32/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.4538A>G | p.Asn1513Ser | missense_variant | 33/43 | ENST00000452625.7 | |
NDE1 | NM_017668.3 | c.948-2708T>C | intron_variant | ENST00000396354.6 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.4517A>G | p.Asn1506Ser | missense_variant | 32/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.4538A>G | p.Asn1513Ser | missense_variant | 33/43 | 1 | NM_001040113.2 | ||
NDE1 | ENST00000396354.6 | c.948-2708T>C | intron_variant | 1 | NM_017668.3 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000342 AC: 5AN: 1461894Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 727248
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 19, 2022 | The p.N1506S variant (also known as c.4517A>G), located in coding exon 31 of the MYH11 gene, results from an A to G substitution at nucleotide position 4517. The asparagine at codon 1506 is replaced by serine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Sep 17, 2023 | This missense variant replaces asparagine with serine at codon 1513 of the MYH11 protein. Computational prediction tool is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Mar 15, 2023 | This missense variant replaces asparagine with serine at codon 1513 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. - |
Aortic aneurysm, familial thoracic 4 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 01, 2021 | This sequence change replaces asparagine with serine at codon 1513 of the MYH11 protein (p.Asn1513Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at