TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2259	7000;7001;7002	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
N2AB	2259	7000;7001;7002	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
N2A	2259	7000;7001;7002	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
N2B	2213	6862;6863;6864	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
Novex-1	2213	6862;6863;6864	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
Novex-2	2213	6862;6863;6864	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661
Novex-3	2259	7000;7001;7002	chr2:178774936;178774935;178774934	chr2:179639663;179639662;179639661

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-11
• Domain position: 86
• Structural Position: 173
• Q(SASA): 0.4352
• 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/E	None	None	0.961	N	0.593	0.355	0.341934017632	gnomAD-4.0.0	2.05276E-06	None	None	None	None	N	None	0	0	None	0	2.52245E-05	None	0	0	1.79882E-06	0	0
K/Q	None	None	0.961	N	0.631	0.319	0.244539031024	gnomAD-4.0.0	6.84252E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99408E-07	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	0.4963	ambiguous	0.4955	ambiguous	-0.683	Destabilizing	0.97	D	0.666	neutral	None	None	None	None	N
K/C	0.7591	likely_pathogenic	0.7359	pathogenic	-0.682	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.776	likely_pathogenic	0.7909	pathogenic	-0.226	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
K/E	0.2725	likely_benign	0.295	benign	-0.106	Destabilizing	0.961	D	0.593	neutral	N	0.500670191	None	None	N
K/F	0.8355	likely_pathogenic	0.8376	pathogenic	-0.312	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	N
K/G	0.6537	likely_pathogenic	0.6581	pathogenic	-1.066	Destabilizing	0.985	D	0.707	prob.neutral	None	None	None	None	N
K/H	0.292	likely_benign	0.2848	benign	-1.372	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/I	0.5441	ambiguous	0.5494	ambiguous	0.314	Stabilizing	0.998	D	0.742	deleterious	D	0.567023902	None	None	N
K/L	0.5116	ambiguous	0.5166	ambiguous	0.314	Stabilizing	0.97	D	0.707	prob.neutral	None	None	None	None	N
K/M	0.3434	ambiguous	0.3436	ambiguous	0.214	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
K/N	0.4707	ambiguous	0.4841	ambiguous	-0.603	Destabilizing	0.98	D	0.613	neutral	N	0.511657503	None	None	N
K/P	0.9347	likely_pathogenic	0.9351	pathogenic	0.012	Stabilizing	0.999	D	0.746	deleterious	None	None	None	None	N
K/Q	0.1551	likely_benign	0.156	benign	-0.664	Destabilizing	0.961	D	0.631	neutral	N	0.506290888	None	None	N
K/R	0.0889	likely_benign	0.0888	benign	-0.714	Destabilizing	0.031	N	0.174	neutral	N	0.475610947	None	None	N
K/S	0.487	ambiguous	0.4907	ambiguous	-1.283	Destabilizing	0.985	D	0.575	neutral	None	None	None	None	N
K/T	0.243	likely_benign	0.2444	benign	-0.95	Destabilizing	0.98	D	0.701	prob.neutral	N	0.486883882	None	None	N
K/V	0.4842	ambiguous	0.4839	ambiguous	0.012	Stabilizing	0.996	D	0.705	prob.neutral	None	None	None	None	N
K/W	0.8402	likely_pathogenic	0.8364	pathogenic	-0.17	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
K/Y	0.7239	likely_pathogenic	0.7285	pathogenic	0.107	Stabilizing	0.999	D	0.756	deleterious	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.