TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14982	45169;45170;45171	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
N2AB	13341	40246;40247;40248	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
N2A	12414	37465;37466;37467	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
N2B	5917	17974;17975;17976	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
Novex-1	6042	18349;18350;18351	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
Novex-2	6109	18550;18551;18552	chr2:178621978;178621977;178621976	chr2:179486705;179486704;179486703
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-101
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.5075
• 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
K/R	None	None	0.002	N	0.163	0.156	0.238705975628	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
K/A	0.5421	ambiguous	0.6395	pathogenic	-0.02	Destabilizing	0.688	D	0.435	neutral	None	None	None	None	N
K/C	0.8457	likely_pathogenic	0.8852	pathogenic	-0.596	Destabilizing	0.998	D	0.463	neutral	None	None	None	None	N
K/D	0.851	likely_pathogenic	0.9021	pathogenic	-0.309	Destabilizing	0.915	D	0.441	neutral	None	None	None	None	N
K/E	0.4028	ambiguous	0.4943	ambiguous	-0.302	Destabilizing	0.625	D	0.514	neutral	N	0.473900731	None	None	N
K/F	0.8784	likely_pathogenic	0.9221	pathogenic	-0.336	Destabilizing	0.991	D	0.449	neutral	None	None	None	None	N
K/G	0.5718	likely_pathogenic	0.6721	pathogenic	-0.163	Destabilizing	0.915	D	0.445	neutral	None	None	None	None	N
K/H	0.4887	ambiguous	0.5412	ambiguous	-0.216	Destabilizing	0.974	D	0.443	neutral	None	None	None	None	N
K/I	0.5575	ambiguous	0.6631	pathogenic	0.275	Stabilizing	0.966	D	0.447	neutral	N	0.501264314	None	None	N
K/L	0.5307	ambiguous	0.6305	pathogenic	0.275	Stabilizing	0.842	D	0.445	neutral	None	None	None	None	N
K/M	0.46	ambiguous	0.5602	ambiguous	-0.223	Destabilizing	0.991	D	0.437	neutral	None	None	None	None	N
K/N	0.6883	likely_pathogenic	0.7748	pathogenic	-0.18	Destabilizing	0.801	D	0.436	neutral	N	0.511224395	None	None	N
K/P	0.6832	likely_pathogenic	0.769	pathogenic	0.201	Stabilizing	0.991	D	0.426	neutral	None	None	None	None	N
K/Q	0.2131	likely_benign	0.2495	benign	-0.264	Destabilizing	0.801	D	0.492	neutral	N	0.491835359	None	None	N
K/R	0.0864	likely_benign	0.0899	benign	-0.142	Destabilizing	0.002	N	0.163	neutral	N	0.418285985	None	None	N
K/S	0.6145	likely_pathogenic	0.7043	pathogenic	-0.516	Destabilizing	0.842	D	0.449	neutral	None	None	None	None	N
K/T	0.3058	likely_benign	0.3835	ambiguous	-0.383	Destabilizing	0.891	D	0.429	neutral	N	0.478599515	None	None	N
K/V	0.5123	ambiguous	0.6105	pathogenic	0.201	Stabilizing	0.974	D	0.421	neutral	None	None	None	None	N
K/W	0.8472	likely_pathogenic	0.8905	pathogenic	-0.464	Destabilizing	0.998	D	0.529	neutral	None	None	None	None	N
K/Y	0.8183	likely_pathogenic	0.8723	pathogenic	-0.107	Destabilizing	0.991	D	0.442	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.