rs121908876
Variant summary
Our verdict is Pathogenic. Variant got 12 ACMG points: 12P and 0B. PS1_ModeratePM1PM2PM5PP3_ModeratePP5_Moderate
The NM_000369.5(TSHR):c.1514G>A(p.Ser505Asn) 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 Likely pathogenic (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely pathogenicin UniProt. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S505R) has been classified as Pathogenic.
Frequency
Consequence
NM_000369.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Pathogenic. Variant got 12 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TSHR | NM_000369.5 | c.1514G>A | p.Ser505Asn | missense_variant | 10/10 | ENST00000298171.7 | |
LOC101928462 | XR_001751022.2 | n.487+21621C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TSHR | ENST00000298171.7 | c.1514G>A | p.Ser505Asn | missense_variant | 10/10 | 1 | NM_000369.5 | P1 | |
ENST00000646052.2 | n.510+21621C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 31
GnomAD4 exome Cov.: 31
GnomAD4 genome ? Cov.: 31
ClinVar
Submissions by phenotype
not provided Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | GeneDx | Jun 17, 2022 | Published functional studies demonstrate a gain-of-function effect: constitutively activated cAMP cascade (Holzapfel et al., 1997); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 9360555, 11012571, 16513835, 10482366, 19636218, 15163335) - |
Familial hyperthyroidism due to mutations in TSH receptor Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Nov 01, 1997 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at