TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14416	43471;43472;43473	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
N2AB	12775	38548;38549;38550	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
N2A	11848	35767;35768;35769	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
N2B	5351	16276;16277;16278	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
Novex-1	5476	16651;16652;16653	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
Novex-2	5543	16852;16853;16854	chr2:178632760;178632759;178632758	chr2:179497487;179497486;179497485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-95
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.6845
• 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
D/V	None	None	1.0	D	0.7	0.723	0.786937795147	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
D/A	0.6658	likely_pathogenic	0.7509	pathogenic	-0.4	Destabilizing	1.0	D	0.69	prob.neutral	D	0.681789458	None	None	N
D/C	0.9704	likely_pathogenic	0.9796	pathogenic	-0.136	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
D/E	0.6662	likely_pathogenic	0.6742	pathogenic	-0.39	Destabilizing	1.0	D	0.4	neutral	D	0.741801155	None	None	N
D/F	0.971	likely_pathogenic	0.9798	pathogenic	-0.017	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
D/G	0.6717	likely_pathogenic	0.7552	pathogenic	-0.674	Destabilizing	1.0	D	0.711	prob.delet.	D	0.740746706	None	None	N
D/H	0.8327	likely_pathogenic	0.8755	pathogenic	0.043	Stabilizing	1.0	D	0.636	neutral	D	0.680773611	None	None	N
D/I	0.9382	likely_pathogenic	0.9586	pathogenic	0.297	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
D/K	0.9287	likely_pathogenic	0.9526	pathogenic	0.131	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
D/L	0.9343	likely_pathogenic	0.9532	pathogenic	0.297	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/M	0.9775	likely_pathogenic	0.9828	pathogenic	0.454	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
D/N	0.2697	likely_benign	0.3153	benign	-0.376	Destabilizing	1.0	D	0.622	neutral	D	0.546292911	None	None	N
D/P	0.92	likely_pathogenic	0.9225	pathogenic	0.088	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
D/Q	0.9277	likely_pathogenic	0.9389	pathogenic	-0.28	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
D/R	0.9287	likely_pathogenic	0.9543	pathogenic	0.382	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
D/S	0.4341	ambiguous	0.5075	ambiguous	-0.506	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
D/T	0.7973	likely_pathogenic	0.8406	pathogenic	-0.279	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
D/V	0.832	likely_pathogenic	0.8842	pathogenic	0.088	Stabilizing	1.0	D	0.7	prob.neutral	D	0.680871233	None	None	N
D/W	0.9937	likely_pathogenic	0.9952	pathogenic	0.209	Stabilizing	1.0	D	0.661	neutral	None	None	None	None	N
D/Y	0.7955	likely_pathogenic	0.8704	pathogenic	0.246	Stabilizing	1.0	D	0.661	neutral	D	0.642240393	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.