TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1097	3514;3515;3516	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
N2AB	1097	3514;3515;3516	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
N2A	1097	3514;3515;3516	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
N2B	1051	3376;3377;3378	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
Novex-1	1051	3376;3377;3378	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
Novex-2	1051	3376;3377;3378	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028
Novex-3	1097	3514;3515;3516	chr2:178782303;178782302;178782301	chr2:179647030;179647029;179647028

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-4
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.2079
• 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
G/W	None	None	1.0	N	0.756	0.41	0.571625278582	gnomAD-4.0.0	1.59052E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85649E-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
G/A	0.1108	likely_benign	0.1146	benign	-0.327	Destabilizing	0.315	N	0.528	neutral	N	0.445621618	None	None	I
G/C	0.3002	likely_benign	0.3001	benign	-0.903	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
G/D	0.2152	likely_benign	0.2295	benign	-0.312	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	I
G/E	0.1988	likely_benign	0.2144	benign	-0.463	Destabilizing	0.996	D	0.769	deleterious	N	0.41721622	None	None	I
G/F	0.6051	likely_pathogenic	0.6349	pathogenic	-1.043	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/H	0.4207	ambiguous	0.4361	ambiguous	-0.616	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
G/I	0.3594	ambiguous	0.3866	ambiguous	-0.428	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
G/K	0.3764	ambiguous	0.3952	ambiguous	-0.628	Destabilizing	0.997	D	0.77	deleterious	None	None	None	None	I
G/L	0.4584	ambiguous	0.4857	ambiguous	-0.428	Destabilizing	0.993	D	0.744	deleterious	None	None	None	None	I
G/M	0.4606	ambiguous	0.4835	ambiguous	-0.404	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	I
G/N	0.251	likely_benign	0.2695	benign	-0.331	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	I
G/P	0.9638	likely_pathogenic	0.9738	pathogenic	-0.361	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	I
G/Q	0.2785	likely_benign	0.2856	benign	-0.61	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/R	0.2655	likely_benign	0.2734	benign	-0.289	Destabilizing	0.996	D	0.793	deleterious	N	0.447769323	None	None	I
G/S	0.0817	likely_benign	0.0839	benign	-0.545	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	I
G/T	0.152	likely_benign	0.1629	benign	-0.621	Destabilizing	0.997	D	0.753	deleterious	None	None	None	None	I
G/V	0.2433	likely_benign	0.2607	benign	-0.361	Destabilizing	0.991	D	0.739	prob.delet.	N	0.447982094	None	None	I
G/W	0.5472	ambiguous	0.5835	pathogenic	-1.181	Destabilizing	1.0	D	0.756	deleterious	N	0.435425733	None	None	I
G/Y	0.5155	ambiguous	0.5443	ambiguous	-0.812	Destabilizing	1.0	D	0.745	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.