TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33634	101125;101126;101127	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
N2AB	31993	96202;96203;96204	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
N2A	31066	93421;93422;93423	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
N2B	24569	73930;73931;73932	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
Novex-1	24694	74305;74306;74307	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
Novex-2	24761	74506;74507;74508	chr2:178535715;178535714;178535713	chr2:179400442;179400441;179400440
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-159
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.6019
• 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
D/V	rs763684680	0.288	0.996	N	0.733	0.563	0.638930745872	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
D/V	rs763684680	0.288	0.996	N	0.733	0.563	0.638930745872	gnomAD-4.0.0	1.59133E-06	None	None	None	None	N	None	0	2.28634E-05	None	0	0	None	0	0	0	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
D/A	0.5334	ambiguous	0.3715	ambiguous	-0.228	Destabilizing	0.981	D	0.609	neutral	N	0.44336026	None	None	N
D/C	0.9495	likely_pathogenic	0.8777	pathogenic	-0.09	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
D/E	0.304	likely_benign	0.214	benign	-0.244	Destabilizing	0.072	N	0.297	neutral	N	0.416384302	None	None	N
D/F	0.8867	likely_pathogenic	0.7973	pathogenic	-0.134	Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
D/G	0.6012	likely_pathogenic	0.4577	ambiguous	-0.413	Destabilizing	0.987	D	0.623	neutral	N	0.448075433	None	None	N
D/H	0.7491	likely_pathogenic	0.5911	pathogenic	0.153	Stabilizing	1.0	D	0.679	prob.neutral	N	0.481745289	None	None	N
D/I	0.7541	likely_pathogenic	0.5641	pathogenic	0.207	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
D/K	0.8483	likely_pathogenic	0.6793	pathogenic	0.3	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
D/L	0.7672	likely_pathogenic	0.6141	pathogenic	0.207	Stabilizing	0.999	D	0.732	prob.delet.	None	None	None	None	N
D/M	0.8919	likely_pathogenic	0.7822	pathogenic	0.206	Stabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	N
D/N	0.2987	likely_benign	0.1986	benign	-0.015	Destabilizing	0.994	D	0.577	neutral	N	0.473683167	None	None	N
D/P	0.9882	likely_pathogenic	0.9715	pathogenic	0.083	Stabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
D/Q	0.7177	likely_pathogenic	0.5496	ambiguous	0.021	Stabilizing	0.997	D	0.652	neutral	None	None	None	None	N
D/R	0.8724	likely_pathogenic	0.7473	pathogenic	0.519	Stabilizing	0.999	D	0.703	prob.neutral	None	None	None	None	N
D/S	0.4365	ambiguous	0.2941	benign	-0.125	Destabilizing	0.986	D	0.556	neutral	None	None	None	None	N
D/T	0.6031	likely_pathogenic	0.4237	ambiguous	0.022	Stabilizing	0.995	D	0.671	neutral	None	None	None	None	N
D/V	0.5333	ambiguous	0.3644	ambiguous	0.083	Stabilizing	0.996	D	0.733	prob.delet.	N	0.443322974	None	None	N
D/W	0.9845	likely_pathogenic	0.9667	pathogenic	-0.006	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/Y	0.591	likely_pathogenic	0.4361	ambiguous	0.101	Stabilizing	1.0	D	0.719	prob.delet.	D	0.530576599	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.