TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2882	8869;8870;8871	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
N2AB	2882	8869;8870;8871	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
N2A	2882	8869;8870;8871	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
N2B	2836	8731;8732;8733	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
Novex-1	2836	8731;8732;8733	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
Novex-2	2836	8731;8732;8733	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662
Novex-3	2882	8869;8870;8871	chr2:178769937;178769936;178769935	chr2:179634664;179634663;179634662

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-19
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2149
• 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	None	None	0.046	N	0.28	0.071	0.482500522706	gnomAD-4.0.0	1.20032E-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	0.5562	ambiguous	0.5351	ambiguous	-0.524	Destabilizing	0.91	D	0.481	neutral	None	None	None	None	N
L/C	0.7688	likely_pathogenic	0.7801	pathogenic	0.03	Stabilizing	0.999	D	0.575	neutral	None	None	None	None	N
L/D	0.9637	likely_pathogenic	0.9515	pathogenic	-0.471	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
L/E	0.8077	likely_pathogenic	0.7822	pathogenic	-0.56	Destabilizing	0.993	D	0.711	prob.delet.	None	None	None	None	N
L/F	0.4722	ambiguous	0.446	ambiguous	-0.669	Destabilizing	0.982	D	0.547	neutral	D	0.565786243	None	None	N
L/G	0.8786	likely_pathogenic	0.8618	pathogenic	-0.699	Destabilizing	0.993	D	0.708	prob.delet.	None	None	None	None	N
L/H	0.6991	likely_pathogenic	0.6684	pathogenic	-0.292	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
L/I	0.1012	likely_benign	0.1014	benign	-0.171	Destabilizing	0.046	N	0.295	neutral	N	0.45486183	None	None	N
L/K	0.6483	likely_pathogenic	0.6404	pathogenic	-0.169	Destabilizing	0.993	D	0.64	neutral	None	None	None	None	N
L/M	0.1904	likely_benign	0.2022	benign	-0.122	Destabilizing	0.986	D	0.551	neutral	None	None	None	None	N
L/N	0.8096	likely_pathogenic	0.7816	pathogenic	0.31	Stabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	N
L/P	0.6181	likely_pathogenic	0.5484	ambiguous	-0.258	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
L/Q	0.507	ambiguous	0.491	ambiguous	0.066	Stabilizing	0.998	D	0.645	neutral	None	None	None	None	N
L/R	0.5448	ambiguous	0.5144	ambiguous	0.281	Stabilizing	0.993	D	0.65	neutral	None	None	None	None	N
L/S	0.73	likely_pathogenic	0.6796	pathogenic	-0.007	Destabilizing	0.991	D	0.638	neutral	D	0.56462952	None	None	N
L/T	0.5063	ambiguous	0.4747	ambiguous	None	Stabilizing	0.986	D	0.506	neutral	None	None	None	None	N
L/V	0.1034	likely_benign	0.0984	benign	-0.258	Destabilizing	0.046	N	0.28	neutral	N	0.492885905	None	None	N
L/W	0.7333	likely_pathogenic	0.7161	pathogenic	-0.755	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
L/Y	0.785	likely_pathogenic	0.7899	pathogenic	-0.473	Destabilizing	0.993	D	0.57	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.