TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20051	60376;60377;60378	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
N2AB	18410	55453;55454;55455	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
N2A	17483	52672;52673;52674	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
N2B	10986	33181;33182;33183	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
Novex-1	11111	33556;33557;33558	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
Novex-2	11178	33757;33758;33759	chr2:178591668;178591667;178591666	chr2:179456395;179456394;179456393
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: Fn3-33
• Domain position: 75
• Structural Position: 109
• Q(SASA): 0.1282
• Predicted PPI site: I

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	0.001	N	0.285	0.057	0.188950314367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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	0.6588	likely_pathogenic	0.6953	pathogenic	-1.218	Destabilizing	0.575	D	0.647	neutral	None	None	None	None	I
K/C	0.695	likely_pathogenic	0.6955	pathogenic	-1.519	Destabilizing	0.991	D	0.798	deleterious	None	None	None	None	I
K/D	0.9693	likely_pathogenic	0.9775	pathogenic	-1.691	Destabilizing	0.826	D	0.667	neutral	None	None	None	None	I
K/E	0.6153	likely_pathogenic	0.6608	pathogenic	-1.456	Destabilizing	0.338	N	0.649	neutral	N	0.478610487	None	None	I
K/F	0.8777	likely_pathogenic	0.9033	pathogenic	-0.465	Destabilizing	0.906	D	0.807	deleterious	None	None	None	None	I
K/G	0.8529	likely_pathogenic	0.8831	pathogenic	-1.663	Destabilizing	0.575	D	0.659	neutral	None	None	None	None	I
K/H	0.524	ambiguous	0.5861	pathogenic	-1.918	Destabilizing	0.906	D	0.713	prob.delet.	None	None	None	None	I
K/I	0.5775	likely_pathogenic	0.6199	pathogenic	0.014	Stabilizing	0.879	D	0.8	deleterious	N	0.46695669	None	None	I
K/L	0.5783	likely_pathogenic	0.6271	pathogenic	0.014	Stabilizing	0.575	D	0.659	neutral	None	None	None	None	I
K/M	0.298	likely_benign	0.3238	benign	-0.356	Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	I
K/N	0.8826	likely_pathogenic	0.91	pathogenic	-1.753	Destabilizing	0.505	D	0.625	neutral	N	0.475104994	None	None	I
K/P	0.9961	likely_pathogenic	0.9974	pathogenic	-0.372	Destabilizing	0.906	D	0.69	prob.neutral	None	None	None	None	I
K/Q	0.2438	likely_benign	0.2742	benign	-1.509	Destabilizing	0.505	D	0.633	neutral	N	0.502162555	None	None	I
K/R	0.1003	likely_benign	0.1011	benign	-1.423	Destabilizing	0.001	N	0.285	neutral	N	0.405233441	None	None	I
K/S	0.7234	likely_pathogenic	0.7689	pathogenic	-2.237	Highly Destabilizing	0.575	D	0.609	neutral	None	None	None	None	I
K/T	0.4168	ambiguous	0.4744	ambiguous	-1.774	Destabilizing	0.505	D	0.647	neutral	N	0.472189152	None	None	I
K/V	0.5261	ambiguous	0.5475	ambiguous	-0.372	Destabilizing	0.826	D	0.694	prob.neutral	None	None	None	None	I
K/W	0.8718	likely_pathogenic	0.8982	pathogenic	-0.559	Destabilizing	0.991	D	0.761	deleterious	None	None	None	None	I
K/Y	0.781	likely_pathogenic	0.8083	pathogenic	-0.206	Destabilizing	0.906	D	0.768	deleterious	None	None	None	None	I

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.