rs201193346
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_002471.4(MYH6):c.2614C>T(p.Arg872Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000466 in 1,614,172 control chromosomes in the GnomAD database, including 1 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R872H) has been classified as Uncertain significance.
Frequency
Consequence
NM_002471.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH6 | NM_002471.4 | c.2614C>T | p.Arg872Cys | missense_variant | 21/39 | ENST00000405093.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH6 | ENST00000405093.9 | c.2614C>T | p.Arg872Cys | missense_variant | 21/39 | 5 | NM_002471.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000263 AC: 40AN: 152174Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000314 AC: 79AN: 251458Hom.: 0 AF XY: 0.000375 AC XY: 51AN XY: 135908
GnomAD4 exome AF: 0.000486 AC: 711AN: 1461880Hom.: 1 Cov.: 33 AF XY: 0.000468 AC XY: 340AN XY: 727242
GnomAD4 genome ? AF: 0.000269 AC: 41AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74466
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | MYH6: BS1 - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Jul 13, 2023 | Reported in association with DCM, though patient-specific details were not described (Haas et al., 2015; Verdonschot et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 25163546, 32880476) - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 30, 2014 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg872Cys var iant in MYH6 has been identified by our laboratory in 1 Caucasian adult with DCM who also carried a likely pathogenic variant in another gene. This variant has been identified in 0.03% (19/67688) of European chromosomes and 0.1% (18/16628) South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac. broadinstitute.org; dbSNP rs201193346). Computational prediction tools suggest t hat this variant may impact the protein, though this information is not predicti ve enough to determine pathogenicity. In summary, while the clinical significanc e of the p.Arg872Cys variant is uncertain, its frequency suggests that it is mor e likely to be benign. - |
Primary dilated cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | research | Genetics and Genomics Program, Sidra Medicine | - | - - |
Hypertrophic cardiomyopathy 14 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Feb 27, 2018 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 08, 2021 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at