TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18350	55273;55274;55275	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
N2AB	16709	50350;50351;50352	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
N2A	15782	47569;47570;47571	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
N2B	9285	28078;28079;28080	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
Novex-1	9410	28453;28454;28455	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
Novex-2	9477	28654;28655;28656	chr2:178602354;178602353;178602352	chr2:179467081;179467080;179467079
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-21
• Domain position: 79
• Structural Position: 109
• Q(SASA): 0.1341
• 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
K/E	None	None	0.92	N	0.751	0.233	0.26169431596	gnomAD-4.0.0	6.00162E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.56252E-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
K/A	0.5819	likely_pathogenic	0.5471	ambiguous	-1.213	Destabilizing	0.863	D	0.703	prob.neutral	None	None	None	None	N
K/C	0.5996	likely_pathogenic	0.6273	pathogenic	-1.692	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
K/D	0.9455	likely_pathogenic	0.9366	pathogenic	-1.997	Destabilizing	0.991	D	0.686	prob.neutral	None	None	None	None	N
K/E	0.5063	ambiguous	0.4835	ambiguous	-1.782	Destabilizing	0.92	D	0.751	deleterious	N	0.498490319	None	None	N
K/F	0.7984	likely_pathogenic	0.762	pathogenic	-0.588	Destabilizing	0.991	D	0.724	prob.delet.	None	None	None	None	N
K/G	0.8403	likely_pathogenic	0.8028	pathogenic	-1.603	Destabilizing	0.969	D	0.686	prob.neutral	None	None	None	None	N
K/H	0.4933	ambiguous	0.4696	ambiguous	-1.912	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
K/I	0.3435	ambiguous	0.3468	ambiguous	-0.143	Destabilizing	0.134	N	0.612	neutral	N	0.440020805	None	None	N
K/L	0.3994	ambiguous	0.4068	ambiguous	-0.143	Destabilizing	0.759	D	0.697	prob.neutral	None	None	None	None	N
K/M	0.2149	likely_benign	0.2279	benign	-0.594	Destabilizing	0.991	D	0.693	prob.neutral	None	None	None	None	N
K/N	0.7787	likely_pathogenic	0.7582	pathogenic	-1.805	Destabilizing	0.988	D	0.715	prob.delet.	N	0.467040372	None	None	N
K/P	0.9953	likely_pathogenic	0.9945	pathogenic	-0.477	Destabilizing	0.997	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.2806	likely_benign	0.2651	benign	-1.591	Destabilizing	0.976	D	0.734	prob.delet.	N	0.490041407	None	None	N
K/R	0.095	likely_benign	0.0935	benign	-1.469	Destabilizing	0.035	N	0.551	neutral	N	0.358365001	None	None	N
K/S	0.6846	likely_pathogenic	0.6554	pathogenic	-2.189	Highly Destabilizing	0.969	D	0.722	prob.delet.	None	None	None	None	N
K/T	0.208	likely_benign	0.2351	benign	-1.771	Destabilizing	0.959	D	0.685	prob.neutral	N	0.436903142	None	None	N
K/V	0.3161	likely_benign	0.3409	ambiguous	-0.477	Destabilizing	0.759	D	0.697	prob.neutral	None	None	None	None	N
K/W	0.8375	likely_pathogenic	0.8152	pathogenic	-0.757	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/Y	0.7442	likely_pathogenic	0.6975	pathogenic	-0.367	Destabilizing	0.997	D	0.701	prob.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.