TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2894	8905;8906;8907	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
N2AB	2894	8905;8906;8907	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
N2A	2894	8905;8906;8907	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
N2B	2848	8767;8768;8769	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
Novex-1	2848	8767;8768;8769	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
Novex-2	2848	8767;8768;8769	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626
Novex-3	2894	8905;8906;8907	chr2:178769901;178769900;178769899	chr2:179634628;179634627;179634626

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-19
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.1129
• 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
P/L	None	None	0.999	N	0.734	0.461	0.754003673566	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
P/A	0.1383	likely_benign	0.1532	benign	-1.327	Destabilizing	0.767	D	0.463	neutral	N	0.458505419	None	None	N
P/C	0.756	likely_pathogenic	0.8598	pathogenic	-0.859	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
P/D	0.8792	likely_pathogenic	0.9352	pathogenic	-1.405	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
P/E	0.6407	likely_pathogenic	0.7391	pathogenic	-1.474	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
P/F	0.8114	likely_pathogenic	0.8889	pathogenic	-1.261	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
P/G	0.6729	likely_pathogenic	0.7772	pathogenic	-1.563	Destabilizing	0.997	D	0.67	neutral	None	None	None	None	N
P/H	0.5821	likely_pathogenic	0.717	pathogenic	-1.079	Destabilizing	1.0	D	0.722	prob.delet.	N	0.508164819	None	None	N
P/I	0.6391	likely_pathogenic	0.715	pathogenic	-0.805	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
P/K	0.6527	likely_pathogenic	0.7798	pathogenic	-1.1	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
P/L	0.2546	likely_benign	0.3136	benign	-0.805	Destabilizing	0.999	D	0.734	prob.delet.	N	0.497897518	None	None	N
P/M	0.5934	likely_pathogenic	0.6749	pathogenic	-0.514	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
P/N	0.7921	likely_pathogenic	0.8771	pathogenic	-0.823	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/Q	0.4447	ambiguous	0.5604	ambiguous	-1.121	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
P/R	0.4807	ambiguous	0.6283	pathogenic	-0.455	Destabilizing	0.999	D	0.751	deleterious	N	0.503518708	None	None	N
P/S	0.3682	ambiguous	0.4864	ambiguous	-1.232	Destabilizing	0.998	D	0.657	neutral	N	0.471925708	None	None	N
P/T	0.3005	likely_benign	0.3896	ambiguous	-1.21	Destabilizing	0.999	D	0.673	neutral	N	0.487960072	None	None	N
P/V	0.4632	ambiguous	0.5416	ambiguous	-0.945	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
P/W	0.9111	likely_pathogenic	0.9553	pathogenic	-1.365	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
P/Y	0.8087	likely_pathogenic	0.892	pathogenic	-1.103	Destabilizing	1.0	D	0.749	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.