TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14677	44254;44255;44256	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
N2AB	13036	39331;39332;39333	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
N2A	12109	36550;36551;36552	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
N2B	5612	17059;17060;17061	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
Novex-1	5737	17434;17435;17436	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
Novex-2	5804	17635;17636;17637	chr2:178630929;178630928;178630927	chr2:179495656;179495655;179495654
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-98
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.0932
• 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/P	None	None	0.828	N	0.839	0.367	0.538974603628	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
L/V	None	None	None	N	0.133	0.069	0.180583059064	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.4863	ambiguous	0.5188	ambiguous	-1.456	Destabilizing	0.057	N	0.617	neutral	None	None	None	None	N
L/C	0.7329	likely_pathogenic	0.7521	pathogenic	-0.931	Destabilizing	0.96	D	0.685	prob.delet.	None	None	None	None	N
L/D	0.9536	likely_pathogenic	0.9408	pathogenic	-0.704	Destabilizing	0.676	D	0.829	deleterious	None	None	None	None	N
L/E	0.768	likely_pathogenic	0.755	pathogenic	-0.66	Destabilizing	0.676	D	0.799	deleterious	None	None	None	None	N
L/F	0.3026	likely_benign	0.3007	benign	-0.795	Destabilizing	0.507	D	0.729	deleterious	None	None	None	None	N
L/G	0.8572	likely_pathogenic	0.8632	pathogenic	-1.813	Destabilizing	0.507	D	0.788	deleterious	None	None	None	None	N
L/H	0.65	likely_pathogenic	0.6406	pathogenic	-1.034	Destabilizing	0.96	D	0.791	deleterious	None	None	None	None	N
L/I	0.0925	likely_benign	0.098	benign	-0.54	Destabilizing	None	N	0.138	neutral	None	None	None	None	N
L/K	0.6852	likely_pathogenic	0.6907	pathogenic	-1.005	Destabilizing	0.507	D	0.745	deleterious	None	None	None	None	N
L/M	0.1106	likely_benign	0.125	benign	-0.518	Destabilizing	0.003	N	0.293	neutral	N	0.455241123	None	None	N
L/N	0.8044	likely_pathogenic	0.7908	pathogenic	-0.907	Destabilizing	0.676	D	0.851	deleterious	None	None	None	None	N
L/P	0.6047	likely_pathogenic	0.5714	pathogenic	-0.814	Destabilizing	0.828	D	0.839	deleterious	N	0.434608721	None	None	N
L/Q	0.5133	ambiguous	0.5388	ambiguous	-0.991	Destabilizing	0.437	N	0.805	deleterious	N	0.452885699	None	None	N
L/R	0.6107	likely_pathogenic	0.6055	pathogenic	-0.544	Destabilizing	0.437	N	0.783	deleterious	N	0.452885699	None	None	N
L/S	0.715	likely_pathogenic	0.7173	pathogenic	-1.573	Destabilizing	0.227	N	0.708	prob.delet.	None	None	None	None	N
L/T	0.4276	ambiguous	0.4532	ambiguous	-1.408	Destabilizing	0.227	N	0.677	prob.neutral	None	None	None	None	N
L/V	0.1061	likely_benign	0.1218	benign	-0.814	Destabilizing	None	N	0.133	neutral	N	0.341387571	None	None	N
L/W	0.5257	ambiguous	0.4996	ambiguous	-0.917	Destabilizing	0.96	D	0.739	deleterious	None	None	None	None	N
L/Y	0.6887	likely_pathogenic	0.6925	pathogenic	-0.666	Destabilizing	0.676	D	0.747	deleterious	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.