TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15707	47344;47345;47346	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
N2AB	14066	42421;42422;42423	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
N2A	13139	39640;39641;39642	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
N2B	6642	20149;20150;20151	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
Novex-1	6767	20524;20525;20526	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
Novex-2	6834	20725;20726;20727	chr2:178618339;178618338;178618337	chr2:179483066;179483065;179483064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-1
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.2792
• 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
A/V	None	None	0.001	N	0.242	0.062	0.251639045875	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
A/C	0.5448	ambiguous	0.4881	ambiguous	-0.681	Destabilizing	0.947	D	0.706	prob.neutral	None	None	None	None	I
A/D	0.9553	likely_pathogenic	0.9221	pathogenic	-0.776	Destabilizing	0.781	D	0.804	deleterious	N	0.509960795	None	None	I
A/E	0.882	likely_pathogenic	0.8274	pathogenic	-0.754	Destabilizing	0.826	D	0.764	deleterious	None	None	None	None	I
A/F	0.8164	likely_pathogenic	0.7275	pathogenic	-0.687	Destabilizing	0.7	D	0.811	deleterious	None	None	None	None	I
A/G	0.5055	ambiguous	0.4531	ambiguous	-0.985	Destabilizing	0.504	D	0.505	neutral	N	0.500489219	None	None	I
A/H	0.9464	likely_pathogenic	0.9053	pathogenic	-1.186	Destabilizing	0.982	D	0.783	deleterious	None	None	None	None	I
A/I	0.3057	likely_benign	0.3123	benign	0.017	Stabilizing	0.103	N	0.517	neutral	None	None	None	None	I
A/K	0.972	likely_pathogenic	0.9513	pathogenic	-0.94	Destabilizing	0.826	D	0.769	deleterious	None	None	None	None	I
A/L	0.3544	ambiguous	0.3169	benign	0.017	Stabilizing	0.25	N	0.533	neutral	None	None	None	None	I
A/M	0.4823	ambiguous	0.4626	ambiguous	-0.054	Destabilizing	0.898	D	0.794	deleterious	None	None	None	None	I
A/N	0.8565	likely_pathogenic	0.8126	pathogenic	-0.785	Destabilizing	0.935	D	0.812	deleterious	None	None	None	None	I
A/P	0.9152	likely_pathogenic	0.8773	pathogenic	-0.171	Destabilizing	0.916	D	0.803	deleterious	D	0.567974066	None	None	I
A/Q	0.8383	likely_pathogenic	0.7966	pathogenic	-0.826	Destabilizing	0.935	D	0.803	deleterious	None	None	None	None	I
A/R	0.9498	likely_pathogenic	0.9224	pathogenic	-0.756	Destabilizing	0.826	D	0.806	deleterious	None	None	None	None	I
A/S	0.2331	likely_benign	0.2143	benign	-1.193	Destabilizing	0.334	N	0.511	neutral	N	0.471045722	None	None	I
A/T	0.2264	likely_benign	0.2008	benign	-1.059	Destabilizing	0.201	N	0.538	neutral	N	0.468477724	None	None	I
A/V	0.1148	likely_benign	0.1314	benign	-0.171	Destabilizing	0.001	N	0.242	neutral	N	0.369531519	None	None	I
A/W	0.9851	likely_pathogenic	0.967	pathogenic	-1.138	Destabilizing	0.982	D	0.751	deleterious	None	None	None	None	I
A/Y	0.9336	likely_pathogenic	0.8676	pathogenic	-0.645	Destabilizing	0.826	D	0.808	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.