TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23423	70492;70493;70494	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
N2AB	21782	65569;65570;65571	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
N2A	20855	62788;62789;62790	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
N2B	14358	43297;43298;43299	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
Novex-1	14483	43672;43673;43674	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
Novex-2	14550	43873;43874;43875	chr2:178575865;178575864;178575863	chr2:179440592;179440591;179440590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-129
• Domain position: 79
• Structural Position: 165
• Q(SASA): 0.4243
• 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/R	None	None	0.958	N	0.56	0.339	0.330589388543	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
K/A	0.3355	likely_benign	0.3809	ambiguous	-0.064	Destabilizing	0.938	D	0.553	neutral	None	None	None	None	N
K/C	0.561	ambiguous	0.5951	pathogenic	-0.31	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
K/D	0.6406	likely_pathogenic	0.6956	pathogenic	0.111	Stabilizing	0.991	D	0.603	neutral	None	None	None	None	N
K/E	0.1509	likely_benign	0.1712	benign	0.115	Stabilizing	0.958	D	0.559	neutral	N	0.441168103	None	None	N
K/F	0.736	likely_pathogenic	0.7846	pathogenic	-0.299	Destabilizing	0.995	D	0.698	prob.neutral	None	None	None	None	N
K/G	0.4662	ambiguous	0.5298	ambiguous	-0.257	Destabilizing	0.938	D	0.6	neutral	None	None	None	None	N
K/H	0.2988	likely_benign	0.3266	benign	-0.534	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/I	0.3064	likely_benign	0.3334	benign	0.362	Stabilizing	0.995	D	0.699	prob.neutral	None	None	None	None	N
K/L	0.3627	ambiguous	0.4027	ambiguous	0.362	Stabilizing	0.991	D	0.584	neutral	None	None	None	None	N
K/M	0.1885	likely_benign	0.2066	benign	0.199	Stabilizing	0.999	D	0.66	neutral	N	0.491207101	None	None	N
K/N	0.3959	ambiguous	0.4408	ambiguous	0.156	Stabilizing	0.988	D	0.625	neutral	N	0.496523018	None	None	N
K/P	0.9093	likely_pathogenic	0.9259	pathogenic	0.248	Stabilizing	0.995	D	0.656	neutral	None	None	None	None	N
K/Q	0.1048	likely_benign	0.1095	benign	-0.038	Destabilizing	0.988	D	0.659	neutral	N	0.499467045	None	None	N
K/R	0.0836	likely_benign	0.0866	benign	-0.067	Destabilizing	0.958	D	0.56	neutral	N	0.498795042	None	None	N
K/S	0.2901	likely_benign	0.3356	benign	-0.369	Destabilizing	0.288	N	0.396	neutral	None	None	None	None	N
K/T	0.1194	likely_benign	0.1303	benign	-0.217	Destabilizing	0.919	D	0.613	neutral	N	0.47841977	None	None	N
K/V	0.2592	likely_benign	0.2891	benign	0.248	Stabilizing	0.991	D	0.635	neutral	None	None	None	None	N
K/W	0.7826	likely_pathogenic	0.8261	pathogenic	-0.287	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/Y	0.6408	likely_pathogenic	0.6899	pathogenic	0.069	Stabilizing	0.998	D	0.679	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.