rs397516777
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PP2PP3_Moderate
The NM_002471.4(MYH6):c.568C>T(p.Arg190Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,884 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R190H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.568C>T | p.Arg190Cys | missense_variant | 7/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.568C>T | p.Arg190Cys | missense_variant | 7/39 | 5 | NM_002471.4 | P1 | |
MYH6 | ENST00000557461.2 | n.635C>T | non_coding_transcript_exon_variant | 7/14 | 5 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251484Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135916
GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727244
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 10, 2015 | The p.Arg190Cys variant in MYH6 not been identified in any other families with c ardiomyopathy, but has been identified in 2/66728 European chromosomes by the Ex ome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397516 777). Computational prediction tools and conservation analysis suggest that the p.Arg190Cys variant may impact the protein, though this information is not predi ctive enough to determine pathogenicity. In summary, the clinical significance o f the p.Arg190Cys variant is uncertain. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2023 | The c.568C>T (p.R190C) alteration is located in exon 7 (coding exon 5) of the MYH6 gene. This alteration results from a C to T substitution at nucleotide position 568, causing the arginine (R) at amino acid position 190 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at