TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17974	54145;54146;54147	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
N2AB	16333	49222;49223;49224	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
N2A	15406	46441;46442;46443	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
N2B	8909	26950;26951;26952	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
Novex-1	9034	27325;27326;27327	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
Novex-2	9101	27526;27527;27528	chr2:178605257;178605256;178605255	chr2:179469984;179469983;179469982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-114
• Domain position: 7
• Structural Position: 9
• Q(SASA): 0.8679
• 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/H	None	None	1.0	N	0.653	0.3	0.202949470691	gnomAD-4.0.0	6.88925E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.03267E-07	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	0.6138	likely_pathogenic	0.6298	pathogenic	0.139	Stabilizing	1.0	D	0.683	prob.neutral	N	0.491955843	None	None	N
D/C	0.9486	likely_pathogenic	0.9535	pathogenic	0.128	Stabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
D/E	0.3893	ambiguous	0.4053	ambiguous	-0.221	Destabilizing	1.0	D	0.388	neutral	N	0.471463141	None	None	N
D/F	0.9279	likely_pathogenic	0.929	pathogenic	0.114	Stabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
D/G	0.5601	ambiguous	0.5801	pathogenic	-0.007	Destabilizing	1.0	D	0.696	prob.neutral	N	0.501287403	None	None	N
D/H	0.7973	likely_pathogenic	0.8045	pathogenic	0.526	Stabilizing	1.0	D	0.653	neutral	N	0.4513997	None	None	N
D/I	0.8658	likely_pathogenic	0.866	pathogenic	0.454	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
D/K	0.8441	likely_pathogenic	0.846	pathogenic	0.727	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
D/L	0.8441	likely_pathogenic	0.8464	pathogenic	0.454	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/M	0.9205	likely_pathogenic	0.9263	pathogenic	0.325	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
D/N	0.25	likely_benign	0.2723	benign	0.346	Stabilizing	1.0	D	0.62	neutral	N	0.450743939	None	None	N
D/P	0.9036	likely_pathogenic	0.9069	pathogenic	0.37	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
D/Q	0.7732	likely_pathogenic	0.7855	pathogenic	0.383	Stabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
D/R	0.8715	likely_pathogenic	0.8736	pathogenic	0.851	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
D/S	0.4075	ambiguous	0.4366	ambiguous	0.311	Stabilizing	1.0	D	0.644	neutral	None	None	None	None	N
D/T	0.6532	likely_pathogenic	0.6811	pathogenic	0.437	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
D/V	0.7305	likely_pathogenic	0.7365	pathogenic	0.37	Stabilizing	1.0	D	0.737	prob.delet.	N	0.4513997	None	None	N
D/W	0.9827	likely_pathogenic	0.9835	pathogenic	0.166	Stabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
D/Y	0.7119	likely_pathogenic	0.7216	pathogenic	0.354	Stabilizing	1.0	D	0.681	prob.neutral	N	0.470010934	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.