TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19948	60067;60068;60069	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
N2AB	18307	55144;55145;55146	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
N2A	17380	52363;52364;52365	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
N2B	10883	32872;32873;32874	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
Novex-1	11008	33247;33248;33249	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
Novex-2	11075	33448;33449;33450	chr2:178592062;178592061;178592060	chr2:179456789;179456788;179456787
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Fn3-32
• Domain position: 72
• Structural Position: 105
• Q(SASA): 0.1042
• 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/F	None	None	0.317	N	0.696	0.128	0.481246930725	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	0.3247	likely_benign	0.3059	benign	-2.555	Highly Destabilizing	0.035	N	0.67	neutral	None	None	None	None	N
L/C	0.3812	ambiguous	0.3846	ambiguous	-1.443	Destabilizing	0.824	D	0.697	prob.neutral	None	None	None	None	N
L/D	0.8099	likely_pathogenic	0.7864	pathogenic	-3.078	Highly Destabilizing	0.38	N	0.756	deleterious	None	None	None	None	N
L/E	0.4718	ambiguous	0.4378	ambiguous	-2.804	Highly Destabilizing	0.38	N	0.757	deleterious	None	None	None	None	N
L/F	0.1059	likely_benign	0.1071	benign	-1.474	Destabilizing	0.317	N	0.696	prob.neutral	N	0.473362588	None	None	N
L/G	0.6962	likely_pathogenic	0.66	pathogenic	-3.087	Highly Destabilizing	0.149	N	0.739	prob.delet.	None	None	None	None	N
L/H	0.1991	likely_benign	0.1972	benign	-2.731	Highly Destabilizing	0.915	D	0.757	deleterious	N	0.503992139	None	None	N
L/I	0.0861	likely_benign	0.0877	benign	-0.97	Destabilizing	0.009	N	0.611	neutral	N	0.462241517	None	None	N
L/K	0.3332	likely_benign	0.3076	benign	-1.779	Destabilizing	0.149	N	0.725	prob.delet.	None	None	None	None	N
L/M	0.1106	likely_benign	0.1075	benign	-0.991	Destabilizing	0.007	N	0.461	neutral	None	None	None	None	N
L/N	0.5052	ambiguous	0.4822	ambiguous	-2.289	Highly Destabilizing	0.38	N	0.756	deleterious	None	None	None	None	N
L/P	0.968	likely_pathogenic	0.9685	pathogenic	-1.488	Destabilizing	0.484	N	0.767	deleterious	N	0.485104947	None	None	N
L/Q	0.1736	likely_benign	0.1625	benign	-2.035	Highly Destabilizing	0.555	D	0.732	prob.delet.	None	None	None	None	N
L/R	0.2281	likely_benign	0.2149	benign	-1.713	Destabilizing	0.484	N	0.731	prob.delet.	N	0.428782304	None	None	N
L/S	0.3163	likely_benign	0.3086	benign	-2.822	Highly Destabilizing	0.007	N	0.614	neutral	None	None	None	None	N
L/T	0.2441	likely_benign	0.2311	benign	-2.418	Highly Destabilizing	0.002	N	0.542	neutral	None	None	None	None	N
L/V	0.0906	likely_benign	0.0891	benign	-1.488	Destabilizing	None	N	0.332	neutral	N	0.427800869	None	None	N
L/W	0.2447	likely_benign	0.2477	benign	-1.923	Destabilizing	0.935	D	0.718	prob.delet.	None	None	None	None	N
L/Y	0.25	likely_benign	0.247	benign	-1.664	Destabilizing	0.555	D	0.729	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.