TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31687	95284;95285;95286	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
N2AB	30046	90361;90362;90363	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
N2A	29119	87580;87581;87582	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
N2B	22622	68089;68090;68091	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
Novex-1	22747	68464;68465;68466	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
Novex-2	22814	68665;68666;68667	chr2:178546272;178546271;178546270	chr2:179410999;179410998;179410997
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-152
• Domain position: 67
• Structural Position: 155
• Q(SASA): 0.1759
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
T/I	rs1471246687	-0.183	0.061	N	0.275	0.192	0.286848849266	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs1471246687	-0.183	0.061	N	0.275	0.192	0.286848849266	gnomAD-4.0.0	2.73694E-06	None	None	None	None	N	None	0	2.23614E-05	None	0	0	None	0	0	2.69854E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
T/A	0.1069	likely_benign	0.1057	benign	-1.163	Destabilizing	0.826	D	0.464	neutral	N	0.465597297	None	None	N
T/C	0.3094	likely_benign	0.2981	benign	-0.836	Destabilizing	0.1	N	0.385	neutral	None	None	None	None	N
T/D	0.5747	likely_pathogenic	0.5891	pathogenic	-1.173	Destabilizing	0.997	D	0.571	neutral	None	None	None	None	N
T/E	0.3961	ambiguous	0.4024	ambiguous	-1.018	Destabilizing	0.997	D	0.565	neutral	None	None	None	None	N
T/F	0.2446	likely_benign	0.2394	benign	-0.996	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
T/G	0.319	likely_benign	0.3199	benign	-1.544	Destabilizing	0.969	D	0.551	neutral	None	None	None	None	N
T/H	0.2571	likely_benign	0.2561	benign	-1.739	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
T/I	0.1073	likely_benign	0.1077	benign	-0.184	Destabilizing	0.061	N	0.275	neutral	N	0.479530838	None	None	N
T/K	0.2821	likely_benign	0.2879	benign	-0.494	Destabilizing	0.997	D	0.566	neutral	None	None	None	None	N
T/L	0.0954	likely_benign	0.0942	benign	-0.184	Destabilizing	0.759	D	0.456	neutral	None	None	None	None	N
T/M	0.085	likely_benign	0.0837	benign	-0.084	Destabilizing	0.991	D	0.582	neutral	None	None	None	None	N
T/N	0.1758	likely_benign	0.1796	benign	-1.018	Destabilizing	0.996	D	0.548	neutral	N	0.478132144	None	None	N
T/P	0.875	likely_pathogenic	0.8799	pathogenic	-0.479	Destabilizing	0.996	D	0.571	neutral	N	0.501098245	None	None	N
T/Q	0.2386	likely_benign	0.2421	benign	-0.925	Destabilizing	0.997	D	0.589	neutral	None	None	None	None	N
T/R	0.2037	likely_benign	0.2024	benign	-0.613	Destabilizing	0.997	D	0.574	neutral	None	None	None	None	N
T/S	0.1298	likely_benign	0.1273	benign	-1.283	Destabilizing	0.959	D	0.525	neutral	N	0.453787031	None	None	N
T/V	0.0979	likely_benign	0.0958	benign	-0.479	Destabilizing	0.079	N	0.171	neutral	None	None	None	None	N
T/W	0.6097	likely_pathogenic	0.6064	pathogenic	-1.054	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
T/Y	0.2835	likely_benign	0.2798	benign	-0.701	Destabilizing	0.997	D	0.593	neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.