TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16369	49330;49331;49332	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
N2AB	14728	44407;44408;44409	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
N2A	13801	41626;41627;41628	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
N2B	7304	22135;22136;22137	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
Novex-1	7429	22510;22511;22512	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
Novex-2	7496	22711;22712;22713	chr2:178614292;178614291;178614290	chr2:179479019;179479018;179479017
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-6
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.2488
• 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
L/I	None	None	0.027	N	0.439	0.038	0.130388298395	gnomAD-4.0.0	1.59318E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86144E-06	0	0
L/P	None	None	0.741	N	0.609	0.305	0.735914652579	gnomAD-4.0.0	1.59316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86146E-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
L/A	0.2007	likely_benign	0.2035	benign	-2.019	Highly Destabilizing	0.035	N	0.463	neutral	None	None	None	None	N
L/C	0.2904	likely_benign	0.2947	benign	-1.351	Destabilizing	0.935	D	0.54	neutral	None	None	None	None	N
L/D	0.5799	likely_pathogenic	0.6067	pathogenic	-1.973	Destabilizing	0.38	N	0.605	neutral	None	None	None	None	N
L/E	0.315	likely_benign	0.353	ambiguous	-1.96	Destabilizing	0.38	N	0.594	neutral	None	None	None	None	N
L/F	0.0828	likely_benign	0.0842	benign	-1.55	Destabilizing	None	N	0.193	neutral	N	0.460188225	None	None	N
L/G	0.496	ambiguous	0.513	ambiguous	-2.355	Highly Destabilizing	0.149	N	0.588	neutral	None	None	None	None	N
L/H	0.1135	likely_benign	0.1155	benign	-1.547	Destabilizing	0.001	N	0.447	neutral	N	0.460846631	None	None	N
L/I	0.0702	likely_benign	0.0723	benign	-1.145	Destabilizing	0.027	N	0.439	neutral	N	0.419761871	None	None	N
L/K	0.2159	likely_benign	0.2153	benign	-1.379	Destabilizing	0.38	N	0.585	neutral	None	None	None	None	N
L/M	0.0905	likely_benign	0.0937	benign	-0.872	Destabilizing	0.005	N	0.307	neutral	None	None	None	None	N
L/N	0.2229	likely_benign	0.2305	benign	-1.272	Destabilizing	0.38	N	0.607	neutral	None	None	None	None	N
L/P	0.9319	likely_pathogenic	0.938	pathogenic	-1.409	Destabilizing	0.741	D	0.609	neutral	N	0.481150404	None	None	N
L/Q	0.1055	likely_benign	0.1126	benign	-1.502	Destabilizing	0.38	N	0.599	neutral	None	None	None	None	N
L/R	0.1592	likely_benign	0.1531	benign	-0.731	Destabilizing	0.317	N	0.598	neutral	N	0.447971546	None	None	N
L/S	0.1653	likely_benign	0.1727	benign	-1.871	Destabilizing	0.149	N	0.527	neutral	None	None	None	None	N
L/T	0.1192	likely_benign	0.1271	benign	-1.747	Destabilizing	0.149	N	0.475	neutral	None	None	None	None	N
L/V	0.07	likely_benign	0.0715	benign	-1.409	Destabilizing	None	N	0.203	neutral	N	0.368085875	None	None	N
L/W	0.2062	likely_benign	0.2095	benign	-1.643	Destabilizing	0.824	D	0.615	neutral	None	None	None	None	N
L/Y	0.206	likely_benign	0.203	benign	-1.417	Destabilizing	0.081	N	0.488	neutral	None	None	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.