18-31595137-G-A
Variant summary
Our verdict is Pathogenic. The variant received 12 ACMG points: 12P and 0B. PM1PM2PM5PP2PP3_StrongPP5
The NM_000371.4(TTR):c.218G>A(p.Gly73Glu) 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 Pathogenic (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G73R) has been classified as Likely pathogenic.
Frequency
Consequence
NM_000371.4 missense
Scores
Clinical Significance
Conservation
Publications
- amyloidosis, hereditary systemic 1Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
- familial amyloid neuropathyInheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
- hereditary ATTR amyloidosisInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- heart conduction diseaseInheritance: AD Classification: STRONG Submitted by: Genomics England PanelApp
- ATTRV122I amyloidosisInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
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ACMG classification
Our verdict: Pathogenic. The variant received 12 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTR | ENST00000237014.8 | c.218G>A | p.Gly73Glu | missense_variant | Exon 3 of 4 | 1 | NM_000371.4 | ENSP00000237014.4 | ||
TTR | ENST00000649620.1 | c.218G>A | p.Gly73Glu | missense_variant | Exon 5 of 6 | ENSP00000497927.1 | ||||
TTR | ENST00000610404.5 | c.122G>A | p.Gly41Glu | missense_variant | Exon 3 of 4 | 5 | ENSP00000477599.2 | |||
TTR | ENST00000541025.2 | n.244G>A | non_coding_transcript_exon_variant | Exon 3 of 3 | 2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome Cov.: 31
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Amyloidosis, hereditary systemic 1 Pathogenic:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at