TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3880	11863;11864;11865	chr2:178741595;178741594;178741593	chr2:179606322;179606321;179606320
N2AB	3563	10912;10913;10914	chr2:178741595;178741594;178741593	chr2:179606322;179606321;179606320
N2A	None	None	chr2:None	chr2:None
N2B	3517	10774;10775;10776	chr2:178741595;178741594;178741593	chr2:179606322;179606321;179606320
Novex-1	3642	11149;11150;11151	chr2:178741595;178741594;178741593	chr2:179606322;179606321;179606320
Novex-2	3709	11350;11351;11352	chr2:178741595;178741594;178741593	chr2:179606322;179606321;179606320
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-27
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3135
• 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/V	rs762132549	-0.935	0.454	N	0.433	0.114	None	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	9.96E-05	0	None	0	None	0	0	0
L/V	rs762132549	-0.935	0.454	N	0.433	0.114	None	gnomAD-4.0.0	1.59118E-06	None	None	None	None	N	None	0	0	None	4.76644E-05	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
L/A	0.5496	ambiguous	0.4271	ambiguous	-1.474	Destabilizing	0.525	D	0.433	neutral	None	None	None	None	N
L/C	0.7163	likely_pathogenic	0.6259	pathogenic	-0.986	Destabilizing	0.998	D	0.497	neutral	None	None	None	None	N
L/D	0.9047	likely_pathogenic	0.8323	pathogenic	-0.583	Destabilizing	0.842	D	0.623	neutral	None	None	None	None	N
L/E	0.7486	likely_pathogenic	0.61	pathogenic	-0.532	Destabilizing	0.842	D	0.616	neutral	None	None	None	None	N
L/F	0.3214	likely_benign	0.2306	benign	-0.797	Destabilizing	0.949	D	0.502	neutral	None	None	None	None	N
L/G	0.787	likely_pathogenic	0.7025	pathogenic	-1.838	Destabilizing	0.842	D	0.594	neutral	None	None	None	None	N
L/H	0.4812	ambiguous	0.3414	ambiguous	-0.923	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	N
L/I	0.1642	likely_benign	0.124	benign	-0.539	Destabilizing	0.016	N	0.212	neutral	None	None	None	None	N
L/K	0.6517	likely_pathogenic	0.4873	ambiguous	-0.937	Destabilizing	0.842	D	0.589	neutral	None	None	None	None	N
L/M	0.2483	likely_benign	0.1895	benign	-0.545	Destabilizing	0.934	D	0.503	neutral	N	0.509788058	None	None	N
L/N	0.5871	likely_pathogenic	0.529	ambiguous	-0.867	Destabilizing	0.949	D	0.633	neutral	None	None	None	None	N
L/P	0.3438	ambiguous	0.2737	benign	-0.819	Destabilizing	0.005	N	0.351	neutral	N	0.491176686	None	None	N
L/Q	0.4626	ambiguous	0.3116	benign	-0.941	Destabilizing	0.966	D	0.607	neutral	N	0.484527528	None	None	N
L/R	0.4346	ambiguous	0.2961	benign	-0.453	Destabilizing	0.966	D	0.604	neutral	N	0.475839647	None	None	N
L/S	0.5327	ambiguous	0.4029	ambiguous	-1.576	Destabilizing	0.067	N	0.377	neutral	None	None	None	None	N
L/T	0.4551	ambiguous	0.3361	benign	-1.394	Destabilizing	0.029	N	0.164	neutral	None	None	None	None	N
L/V	0.2028	likely_benign	0.1523	benign	-0.819	Destabilizing	0.454	N	0.433	neutral	N	0.503467246	None	None	N
L/W	0.5761	likely_pathogenic	0.4399	ambiguous	-0.879	Destabilizing	0.998	D	0.609	neutral	None	None	None	None	N
L/Y	0.6412	likely_pathogenic	0.5223	ambiguous	-0.641	Destabilizing	0.991	D	0.54	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.