TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	962	3109;3110;3111	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
N2AB	962	3109;3110;3111	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
N2A	962	3109;3110;3111	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
N2B	916	2971;2972;2973	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
Novex-1	916	2971;2972;2973	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
Novex-2	916	2971;2972;2973	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747
Novex-3	962	3109;3110;3111	chr2:178783022;178783021;178783020	chr2:179647749;179647748;179647747

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-3
• Domain position: 20
• Structural Position: 30
• Q(SASA): 0.1517
• 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/W	None	None	0.997	D	0.808	0.754	0.92973120882	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.9853	likely_pathogenic	0.9856	pathogenic	-2.589	Highly Destabilizing	0.86	D	0.692	prob.neutral	None	None	None	None	N
L/C	0.9921	likely_pathogenic	0.9908	pathogenic	-1.898	Destabilizing	0.998	D	0.708	prob.neutral	None	None	None	None	N
L/D	0.9998	likely_pathogenic	0.9998	pathogenic	-3.306	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
L/E	0.9985	likely_pathogenic	0.9987	pathogenic	-3.019	Highly Destabilizing	0.993	D	0.857	deleterious	None	None	None	None	N
L/F	0.6257	likely_pathogenic	0.4067	ambiguous	-1.61	Destabilizing	0.032	N	0.403	neutral	D	0.527357581	None	None	N
L/G	0.9979	likely_pathogenic	0.9978	pathogenic	-3.149	Highly Destabilizing	0.978	D	0.857	deleterious	None	None	None	None	N
L/H	0.9968	likely_pathogenic	0.9956	pathogenic	-2.68	Highly Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
L/I	0.4781	ambiguous	0.4465	ambiguous	-0.923	Destabilizing	0.754	D	0.604	neutral	None	None	None	None	N
L/K	0.996	likely_pathogenic	0.9962	pathogenic	-2.12	Highly Destabilizing	0.978	D	0.843	deleterious	None	None	None	None	N
L/M	0.4478	ambiguous	0.4151	ambiguous	-0.962	Destabilizing	0.489	N	0.528	neutral	D	0.540897858	None	None	N
L/N	0.9992	likely_pathogenic	0.9991	pathogenic	-2.685	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
L/P	0.999	likely_pathogenic	0.9991	pathogenic	-1.467	Destabilizing	0.993	D	0.86	deleterious	None	None	None	None	N
L/Q	0.9946	likely_pathogenic	0.9945	pathogenic	-2.437	Highly Destabilizing	0.978	D	0.859	deleterious	None	None	None	None	N
L/R	0.9923	likely_pathogenic	0.9921	pathogenic	-2.064	Highly Destabilizing	0.978	D	0.852	deleterious	None	None	None	None	N
L/S	0.9987	likely_pathogenic	0.9987	pathogenic	-3.281	Highly Destabilizing	0.971	D	0.834	deleterious	D	0.789501895	None	None	N
L/T	0.9927	likely_pathogenic	0.9935	pathogenic	-2.833	Highly Destabilizing	0.978	D	0.728	prob.delet.	None	None	None	None	N
L/V	0.6131	likely_pathogenic	0.6094	pathogenic	-1.467	Destabilizing	0.698	D	0.648	neutral	D	0.652121517	None	None	N
L/W	0.9745	likely_pathogenic	0.9586	pathogenic	-1.979	Destabilizing	0.997	D	0.808	deleterious	D	0.718266326	None	None	N
L/Y	0.9827	likely_pathogenic	0.9668	pathogenic	-1.703	Destabilizing	0.915	D	0.739	prob.delet.	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.