rs750341311
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PP2PP3_ModerateBS2
The NM_002471.4(MYH6):āc.756C>Gā(p.His252Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,668 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. H252Y) has been classified as Uncertain significance.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.756C>G | p.His252Gln | missense_variant | 9/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.756C>G | p.His252Gln | missense_variant | 9/39 | 5 | NM_002471.4 | P1 | |
MYH6 | ENST00000557461.2 | n.823C>G | non_coding_transcript_exon_variant | 9/14 | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248202Hom.: 0 AF XY: 0.0000298 AC XY: 4AN XY: 134150
GnomAD4 exome AF: 0.0000178 AC: 26AN: 1460478Hom.: 0 Cov.: 32 AF XY: 0.0000138 AC XY: 10AN XY: 726376
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152190Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74346
ClinVar
Submissions by phenotype
Hypertrophic cardiomyopathy 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 14, 2023 | ClinVar contains an entry for this variant (Variation ID: 537949). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on MYH6 function (PMID: 20656787). 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 MYH6 protein function. This missense change has been observed in individual(s) with transposition of the great arteries, sudden infant death syndrome, and left ventricular noncompaction (PMID: 20656787, 26350513, 33082984). This variant is present in population databases (rs750341311, gnomAD 0.004%). This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 252 of the MYH6 protein (p.His252Gln). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | AiLife Diagnostics, AiLife Diagnostics | Dec 15, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at