chr14-23419182-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_000257.4(MYH7):c.3967G>A(p.Val1323Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,812 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_000257.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.3967G>A | p.Val1323Ile | missense_variant | 29/40 | ENST00000355349.4 | |
MYH7 | NM_001407004.1 | c.3967G>A | p.Val1323Ile | missense_variant | 28/39 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.3967G>A | p.Val1323Ile | missense_variant | 29/40 | 1 | NM_000257.4 | P1 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461812Hom.: 0 Cov.: 33 AF XY: 0.00000275 AC XY: 2AN XY: 727214
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 | Oct 21, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Val1323Ile vari ant in MYH7 has now been identified by our laboratory in 1 Caucasian individual with HCM. It has not been identified in large population studies. Valine (Val) a t position 1323 is not conserved in mammals or evolutionarily distant species an d the change to isoleucine (Ile; this variant) has been identified in two fish s pecies. Additionally, this variant was predicted to be benign using a computatio nal tool clinically validated by our laboratory. This tool's benign prediction i s estimated to be correct 89% of the time (Jordan 2011). Although this data supp orts that the Val1323Ile variant may be benign, additional studies are needed to fully assess its clinical significance. - |
Cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Nov 30, 2023 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at