TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23380	70363;70364;70365	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
N2AB	21739	65440;65441;65442	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
N2A	20812	62659;62660;62661	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
N2B	14315	43168;43169;43170	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
Novex-1	14440	43543;43544;43545	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
Novex-2	14507	43744;43745;43746	chr2:178575994;178575993;178575992	chr2:179440721;179440720;179440719
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-129
• Domain position: 36
• Structural Position: 50
• Q(SASA): 0.1428
• 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	0.999	N	0.575	0.339	0.18995819373	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	0.9608	likely_pathogenic	0.974	pathogenic	-1.064	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
K/C	0.9553	likely_pathogenic	0.9617	pathogenic	-1.124	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/D	0.993	likely_pathogenic	0.9953	pathogenic	-0.462	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/E	0.9226	likely_pathogenic	0.9536	pathogenic	-0.28	Destabilizing	0.999	D	0.556	neutral	N	0.512497911	None	None	N
K/F	0.9852	likely_pathogenic	0.988	pathogenic	-0.691	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/G	0.9765	likely_pathogenic	0.9843	pathogenic	-1.481	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/H	0.8085	likely_pathogenic	0.8187	pathogenic	-1.772	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/I	0.9274	likely_pathogenic	0.9505	pathogenic	0.056	Stabilizing	1.0	D	0.827	deleterious	N	0.511230463	None	None	N
K/L	0.9156	likely_pathogenic	0.932	pathogenic	0.056	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/M	0.8237	likely_pathogenic	0.8567	pathogenic	-0.075	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
K/N	0.9794	likely_pathogenic	0.9856	pathogenic	-0.893	Destabilizing	1.0	D	0.735	prob.delet.	N	0.494140166	None	None	N
K/P	0.9946	likely_pathogenic	0.9966	pathogenic	-0.289	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
K/Q	0.6911	likely_pathogenic	0.7594	pathogenic	-0.861	Destabilizing	1.0	D	0.723	prob.delet.	N	0.500216553	None	None	N
K/R	0.1092	likely_benign	0.1205	benign	-0.758	Destabilizing	0.999	D	0.575	neutral	N	0.475010452	None	None	N
K/S	0.9782	likely_pathogenic	0.986	pathogenic	-1.658	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/T	0.9264	likely_pathogenic	0.9547	pathogenic	-1.236	Destabilizing	1.0	D	0.777	deleterious	N	0.511990932	None	None	N
K/V	0.8843	likely_pathogenic	0.9118	pathogenic	-0.289	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/W	0.9709	likely_pathogenic	0.9777	pathogenic	-0.542	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
K/Y	0.954	likely_pathogenic	0.959	pathogenic	-0.214	Destabilizing	1.0	D	0.806	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.