TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2692	8299;8300;8301	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
N2AB	2692	8299;8300;8301	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
N2A	2692	8299;8300;8301	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
N2B	2646	8161;8162;8163	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
Novex-1	2646	8161;8162;8163	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
Novex-2	2646	8161;8162;8163	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978
Novex-3	2692	8299;8300;8301	chr2:178771253;178771252;178771251	chr2:179635980;179635979;179635978

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-16
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.3002
• 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/N	None	None	0.175	N	0.449	0.154	0.166414681773	gnomAD-4.0.0	8.20914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.89234E-06	0	1.65574E-05

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	0.2459	likely_benign	0.2827	benign	-0.925	Destabilizing	0.055	N	0.389	neutral	None	None	None	None	N
K/C	0.5777	likely_pathogenic	0.5941	pathogenic	-0.992	Destabilizing	0.958	D	0.507	neutral	None	None	None	None	N
K/D	0.4965	ambiguous	0.5301	ambiguous	-0.3	Destabilizing	0.055	N	0.455	neutral	None	None	None	None	N
K/E	0.1054	likely_benign	0.12	benign	-0.134	Destabilizing	None	N	0.213	neutral	N	0.443152398	None	None	N
K/F	0.6534	likely_pathogenic	0.6844	pathogenic	-0.459	Destabilizing	0.859	D	0.522	neutral	None	None	None	None	N
K/G	0.435	ambiguous	0.4887	ambiguous	-1.335	Destabilizing	None	N	0.414	neutral	None	None	None	None	N
K/H	0.2295	likely_benign	0.2397	benign	-1.557	Destabilizing	0.497	N	0.519	neutral	None	None	None	None	N
K/I	0.2041	likely_benign	0.2224	benign	0.167	Stabilizing	0.667	D	0.569	neutral	None	None	None	None	N
K/L	0.2384	likely_benign	0.2557	benign	0.167	Stabilizing	0.22	N	0.51	neutral	None	None	None	None	N
K/M	0.1487	likely_benign	0.1609	benign	-0.022	Destabilizing	0.602	D	0.517	neutral	N	0.512950813	None	None	N
K/N	0.2915	likely_benign	0.3281	benign	-0.798	Destabilizing	0.175	N	0.449	neutral	N	0.511214043	None	None	N
K/P	0.9573	likely_pathogenic	0.9576	pathogenic	-0.169	Destabilizing	0.364	N	0.534	neutral	None	None	None	None	N
K/Q	0.0875	likely_benign	0.0973	benign	-0.791	Destabilizing	None	N	0.194	neutral	N	0.440183691	None	None	N
K/R	0.0777	likely_benign	0.0784	benign	-0.733	Destabilizing	0.001	N	0.179	neutral	N	0.484837895	None	None	N
K/S	0.2873	likely_benign	0.3228	benign	-1.546	Destabilizing	0.055	N	0.41	neutral	None	None	None	None	N
K/T	0.0996	likely_benign	0.113	benign	-1.15	Destabilizing	0.175	N	0.489	neutral	N	0.503351756	None	None	N
K/V	0.1948	likely_benign	0.2148	benign	-0.169	Destabilizing	0.22	N	0.53	neutral	None	None	None	None	N
K/W	0.6745	likely_pathogenic	0.6976	pathogenic	-0.298	Destabilizing	0.958	D	0.506	neutral	None	None	None	None	N
K/Y	0.5277	ambiguous	0.5429	ambiguous	None	Stabilizing	0.667	D	0.559	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.