rs552818350
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_002474.3(MYH11):c.3560C>T(p.Thr1187Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000142 in 1,614,210 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. T1187T) has been classified as Likely benign.
Frequency
Consequence
NM_002474.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH11 | NM_002474.3 | c.3560C>T | p.Thr1187Met | missense_variant | 27/41 | ENST00000300036.6 | |
MYH11 | NM_001040113.2 | c.3581C>T | p.Thr1194Met | missense_variant | 28/43 | ENST00000452625.7 | |
MYH11 | NM_001040114.2 | c.3581C>T | p.Thr1194Met | missense_variant | 28/42 | ||
MYH11 | NM_022844.3 | c.3560C>T | p.Thr1187Met | missense_variant | 27/42 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH11 | ENST00000300036.6 | c.3560C>T | p.Thr1187Met | missense_variant | 27/41 | 1 | NM_002474.3 | P3 | |
MYH11 | ENST00000452625.7 | c.3581C>T | p.Thr1194Met | missense_variant | 28/43 | 1 | NM_001040113.2 | ||
ENST00000574212.1 | n.498G>A | non_coding_transcript_exon_variant | 2/2 | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251450Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135896
GnomAD4 exome AF: 0.0000116 AC: 17AN: 1461894Hom.: 0 Cov.: 31 AF XY: 0.0000110 AC XY: 8AN XY: 727248
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152316Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74482
ClinVar
Submissions by phenotype
Familial thoracic aortic aneurysm and aortic dissection Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 15, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Nov 15, 2022 | This missense variant replaces threonine with methionine at codon 1194 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 been identified in 3/251450 chromosomes 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 | Nov 03, 2023 | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1194 of the MYH11 protein (p.Thr1194Met). This variant is present in population databases (rs552818350, gnomAD 0.007%). This missense change has been observed in individuals with MYH11-related disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 405474). 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 MYH11 protein function with a negative predictive value of 95%. 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. - |
Bicuspid aortic valve Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Molecular Genetics Laboratory, Johns Hopkins All Children's Hospital | Nov 19, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at