TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22284	67075;67076;67077	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
N2AB	20643	62152;62153;62154	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
N2A	19716	59371;59372;59373	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
N2B	13219	39880;39881;39882	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
Novex-1	13344	40255;40256;40257	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
Novex-2	13411	40456;40457;40458	chr2:178580529;178580528;178580527	chr2:179445256;179445255;179445254
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-126
• Domain position: 20
• Structural Position: 34
• Q(SASA): 0.3899
• 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
P/L	None	None	0.797	N	0.691	0.352	0.700453235612	gnomAD-4.0.0	6.16186E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39901E-06	2.31992E-05	1.65854E-05
P/S	None	None	0.994	N	0.745	0.271	0.470155540985	gnomAD-4.0.0	1.36929E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.31986E-05	0
P/T	None	None	0.988	N	0.717	0.27	0.487772906946	gnomAD-4.0.0	6.84644E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99821E-07	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
P/A	0.2041	likely_benign	0.1723	benign	-0.964	Destabilizing	0.958	D	0.647	neutral	N	0.486880871	None	None	I
P/C	0.8419	likely_pathogenic	0.8024	pathogenic	-0.657	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
P/D	0.8941	likely_pathogenic	0.8702	pathogenic	-0.875	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	I
P/E	0.76	likely_pathogenic	0.6988	pathogenic	-0.914	Destabilizing	0.998	D	0.756	deleterious	None	None	None	None	I
P/F	0.9061	likely_pathogenic	0.8529	pathogenic	-0.84	Destabilizing	0.998	D	0.745	deleterious	None	None	None	None	I
P/G	0.6349	likely_pathogenic	0.5684	pathogenic	-1.201	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	I
P/H	0.6399	likely_pathogenic	0.5585	ambiguous	-0.666	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
P/I	0.7283	likely_pathogenic	0.6213	pathogenic	-0.442	Destabilizing	0.334	N	0.609	neutral	None	None	None	None	I
P/K	0.6893	likely_pathogenic	0.6469	pathogenic	-0.86	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	I
P/L	0.4094	ambiguous	0.2979	benign	-0.442	Destabilizing	0.797	D	0.691	prob.neutral	N	0.488401808	None	None	I
P/M	0.6799	likely_pathogenic	0.5775	pathogenic	-0.444	Destabilizing	0.998	D	0.731	prob.delet.	None	None	None	None	I
P/N	0.7465	likely_pathogenic	0.6871	pathogenic	-0.65	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	I
P/Q	0.5322	ambiguous	0.4582	ambiguous	-0.84	Destabilizing	0.998	D	0.758	deleterious	D	0.533094043	None	None	I
P/R	0.553	ambiguous	0.4996	ambiguous	-0.308	Destabilizing	0.998	D	0.747	deleterious	D	0.522031687	None	None	I
P/S	0.4099	ambiguous	0.3479	ambiguous	-1.043	Destabilizing	0.994	D	0.745	deleterious	N	0.496173237	None	None	I
P/T	0.3094	likely_benign	0.2542	benign	-0.977	Destabilizing	0.988	D	0.717	prob.delet.	N	0.495786448	None	None	I
P/V	0.5394	ambiguous	0.4424	ambiguous	-0.581	Destabilizing	0.839	D	0.639	neutral	None	None	None	None	I
P/W	0.9503	likely_pathogenic	0.9216	pathogenic	-0.993	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
P/Y	0.8833	likely_pathogenic	0.8389	pathogenic	-0.696	Destabilizing	0.999	D	0.741	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.