rs1060503168
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_Strong
The NM_001927.4(DES):c.986A>C(p.Gln329Pro) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. Q329R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001927.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DES | NM_001927.4 | c.986A>C | p.Gln329Pro | missense_variant | 5/9 | ENST00000373960.4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DES | ENST00000373960.4 | c.986A>C | p.Gln329Pro | missense_variant | 5/9 | 1 | NM_001927.4 | P1 | |
DES | ENST00000477226.6 | n.460A>C | non_coding_transcript_exon_variant | 4/8 | 4 | ||||
DES | ENST00000492726.1 | n.381A>C | non_coding_transcript_exon_variant | 4/6 | 4 | ||||
DES | ENST00000683013.1 | n.374A>C | non_coding_transcript_exon_variant | 3/7 |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 38
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
Desmin-related myofibrillar myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 04, 2021 | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 411142). This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 329 of the DES protein (p.Gln329Pro). 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. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Sep 12, 2016 | The Q329P variant of uncertain significance in the DES gene has not been published as a pathogenic or benign variant to our knowledge. This variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The Q329P variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution also occurs at a position that is conserved across species. Consequently, in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, additional evidence is needed to determine whether the Q329P variant in the DES gene is pathogenic or benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at