TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20339	61240;61241;61242	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
N2AB	18698	56317;56318;56319	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
N2A	17771	53536;53537;53538	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
N2B	11274	34045;34046;34047	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
Novex-1	11399	34420;34421;34422	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
Novex-2	11466	34621;34622;34623	chr2:178590710;178590709;178590708	chr2:179455437;179455436;179455435
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-35
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.168
• 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
N/K	None	None	0.997	N	0.673	0.251	0.107399877778	gnomAD-4.0.0	1.59306E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86136E-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
N/A	0.359	ambiguous	0.3356	benign	-0.781	Destabilizing	0.91	D	0.585	neutral	None	None	None	None	N
N/C	0.259	likely_benign	0.2472	benign	0.103	Stabilizing	0.128	N	0.431	neutral	None	None	None	None	N
N/D	0.4187	ambiguous	0.3835	ambiguous	-0.036	Destabilizing	0.99	D	0.561	neutral	N	0.482711863	None	None	N
N/E	0.7052	likely_pathogenic	0.6475	pathogenic	0.028	Stabilizing	0.998	D	0.67	neutral	None	None	None	None	N
N/F	0.6487	likely_pathogenic	0.639	pathogenic	-0.643	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
N/G	0.4517	ambiguous	0.4208	ambiguous	-1.082	Destabilizing	0.976	D	0.471	neutral	None	None	None	None	N
N/H	0.1545	likely_benign	0.1458	benign	-0.819	Destabilizing	0.997	D	0.675	prob.neutral	N	0.473093229	None	None	N
N/I	0.2882	likely_benign	0.276	benign	-0.03	Destabilizing	0.982	D	0.732	prob.delet.	N	0.445618626	None	None	N
N/K	0.5441	ambiguous	0.4888	ambiguous	-0.211	Destabilizing	0.997	D	0.673	neutral	N	0.465684467	None	None	N
N/L	0.3205	likely_benign	0.3217	benign	-0.03	Destabilizing	0.973	D	0.719	prob.delet.	None	None	None	None	N
N/M	0.3994	ambiguous	0.4047	ambiguous	0.268	Stabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
N/P	0.9488	likely_pathogenic	0.9458	pathogenic	-0.251	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
N/Q	0.4903	ambiguous	0.4532	ambiguous	-0.632	Destabilizing	0.998	D	0.686	prob.neutral	None	None	None	None	N
N/R	0.5489	ambiguous	0.5009	ambiguous	-0.222	Destabilizing	0.998	D	0.695	prob.neutral	None	None	None	None	N
N/S	0.1206	likely_benign	0.1105	benign	-0.686	Destabilizing	0.939	D	0.473	neutral	N	0.456640909	None	None	N
N/T	0.2294	likely_benign	0.2115	benign	-0.438	Destabilizing	0.939	D	0.595	neutral	N	0.411324333	None	None	N
N/V	0.2883	likely_benign	0.2766	benign	-0.251	Destabilizing	0.986	D	0.748	deleterious	None	None	None	None	N
N/W	0.8725	likely_pathogenic	0.867	pathogenic	-0.457	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
N/Y	0.2539	likely_benign	0.2349	benign	-0.264	Destabilizing	0.997	D	0.725	prob.delet.	N	0.471697953	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.