rs727503306
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_033118.4(MYLK2):āc.1694T>Cā(p.Met565Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000585 in 1,606,716 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_033118.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYLK2 | NM_033118.4 | c.1694T>C | p.Met565Thr | missense_variant | 12/13 | ENST00000375985.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYLK2 | ENST00000375985.5 | c.1694T>C | p.Met565Thr | missense_variant | 12/13 | 1 | NM_033118.4 | P1 | |
MYLK2 | ENST00000375994.6 | c.1694T>C | p.Met565Thr | missense_variant | 11/12 | 1 | P1 | ||
MYLK2 | ENST00000468730.1 | n.632T>C | non_coding_transcript_exon_variant | 5/6 | 1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000264 AC: 4AN: 151266Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000988 AC: 24AN: 242894Hom.: 0 AF XY: 0.000168 AC XY: 22AN XY: 131074
GnomAD4 exome AF: 0.0000618 AC: 90AN: 1455450Hom.: 0 Cov.: 37 AF XY: 0.0000871 AC XY: 63AN XY: 723490
GnomAD4 genome ? AF: 0.0000264 AC: 4AN: 151266Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2AN XY: 73806
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Oct 15, 2013 | The Met565Thr variant in MYLK2 has been identified by our laboratory in 1 Caucas ian individual with DCM and data from large population studies is insufficient t o assess the frequency of this variant. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information i s needed to fully assess the clinical significance of the Met565Thr variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 11, 2022 | The p.M565T variant (also known as c.1694T>C), located in coding exon 11 of the MYLK2 gene, results from a T to C substitution at nucleotide position 1694. The methionine at codon 565 is replaced by threonine, an amino acid with 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. - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Oct 05, 2016 | - - |
Hypertrophic cardiomyopathy 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 02, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at