TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14180	42763;42764;42765	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
N2AB	12539	37840;37841;37842	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
N2A	11612	35059;35060;35061	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
N2B	5115	15568;15569;15570	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
Novex-1	5240	15943;15944;15945	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
Novex-2	5307	16144;16145;16146	chr2:178633961;178633960;178633959	chr2:179498688;179498687;179498686
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-92
• Domain position: 39
• Structural Position: 56
• Q(SASA): 0.7455
• 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	0.982	N	0.573	0.35	0.350088858571	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4556	ambiguous	0.53	ambiguous	-0.499	Destabilizing	0.953	D	0.575	neutral	None	None	None	None	N
K/C	0.8274	likely_pathogenic	0.8529	pathogenic	-0.518	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/D	0.8303	likely_pathogenic	0.8685	pathogenic	-0.195	Destabilizing	0.91	D	0.563	neutral	None	None	None	None	N
K/E	0.275	likely_benign	0.3364	benign	-0.083	Destabilizing	0.17	N	0.321	neutral	N	0.449501153	None	None	N
K/F	0.8541	likely_pathogenic	0.8808	pathogenic	-0.233	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/G	0.7127	likely_pathogenic	0.7668	pathogenic	-0.819	Destabilizing	0.976	D	0.537	neutral	None	None	None	None	N
K/H	0.524	ambiguous	0.5374	ambiguous	-0.901	Destabilizing	0.998	D	0.585	neutral	None	None	None	None	N
K/I	0.3883	ambiguous	0.4379	ambiguous	0.321	Stabilizing	0.991	D	0.671	neutral	N	0.506080659	None	None	N
K/L	0.4226	ambiguous	0.4798	ambiguous	0.321	Stabilizing	0.986	D	0.527	neutral	None	None	None	None	N
K/M	0.3212	likely_benign	0.3673	ambiguous	-0.105	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
K/N	0.6742	likely_pathogenic	0.7089	pathogenic	-0.389	Destabilizing	0.982	D	0.573	neutral	N	0.508716885	None	None	N
K/P	0.4925	ambiguous	0.5875	pathogenic	0.076	Stabilizing	0.998	D	0.614	neutral	None	None	None	None	N
K/Q	0.193	likely_benign	0.2091	benign	-0.37	Destabilizing	0.982	D	0.581	neutral	N	0.503309965	None	None	N
K/R	0.095	likely_benign	0.092	benign	-0.362	Destabilizing	0.1	N	0.311	neutral	N	0.487569141	None	None	N
K/S	0.6305	likely_pathogenic	0.6884	pathogenic	-0.901	Destabilizing	0.953	D	0.571	neutral	None	None	None	None	N
K/T	0.322	likely_benign	0.3689	ambiguous	-0.598	Destabilizing	0.991	D	0.551	neutral	N	0.514296169	None	None	N
K/V	0.364	ambiguous	0.4178	ambiguous	0.076	Stabilizing	0.993	D	0.591	neutral	None	None	None	None	N
K/W	0.8802	likely_pathogenic	0.9005	pathogenic	-0.218	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/Y	0.7651	likely_pathogenic	0.8003	pathogenic	0.059	Stabilizing	0.998	D	0.623	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.