TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3187	9784;9785;9786	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
N2AB	3187	9784;9785;9786	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
N2A	3187	9784;9785;9786	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
N2B	3141	9646;9647;9648	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
Novex-1	3141	9646;9647;9648	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
Novex-2	3141	9646;9647;9648	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250
Novex-3	3187	9784;9785;9786	chr2:178766525;178766524;178766523	chr2:179631252;179631251;179631250

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-22
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.3587
• 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
N/S	None	None	0.826	N	0.4	0.168	0.287603790349	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
N/A	0.4688	ambiguous	0.4358	ambiguous	-0.433	Destabilizing	0.939	D	0.375	neutral	None	None	None	None	N
N/C	0.6479	likely_pathogenic	0.6029	pathogenic	0.183	Stabilizing	0.999	D	0.509	neutral	None	None	None	None	N
N/D	0.2107	likely_benign	0.2272	benign	0.247	Stabilizing	0.035	N	0.141	neutral	N	0.492091264	None	None	N
N/E	0.717	likely_pathogenic	0.7242	pathogenic	0.269	Stabilizing	0.759	D	0.331	neutral	None	None	None	None	N
N/F	0.8373	likely_pathogenic	0.849	pathogenic	-0.586	Destabilizing	0.997	D	0.476	neutral	None	None	None	None	N
N/G	0.6371	likely_pathogenic	0.5798	pathogenic	-0.671	Destabilizing	0.927	D	0.345	neutral	None	None	None	None	N
N/H	0.2253	likely_benign	0.2267	benign	-0.548	Destabilizing	0.988	D	0.407	neutral	N	0.514640214	None	None	N
N/I	0.4166	ambiguous	0.4606	ambiguous	0.121	Stabilizing	0.996	D	0.477	neutral	N	0.515442697	None	None	N
N/K	0.6553	likely_pathogenic	0.689	pathogenic	0.024	Stabilizing	0.852	D	0.33	neutral	N	0.444768845	None	None	N
N/L	0.4395	ambiguous	0.4608	ambiguous	0.121	Stabilizing	0.939	D	0.419	neutral	None	None	None	None	N
N/M	0.6606	likely_pathogenic	0.6663	pathogenic	0.237	Stabilizing	0.999	D	0.446	neutral	None	None	None	None	N
N/P	0.5956	likely_pathogenic	0.553	ambiguous	-0.035	Destabilizing	0.997	D	0.431	neutral	None	None	None	None	N
N/Q	0.6179	likely_pathogenic	0.6	pathogenic	-0.377	Destabilizing	0.373	N	0.138	neutral	None	None	None	None	N
N/R	0.6206	likely_pathogenic	0.6543	pathogenic	0.01	Stabilizing	0.939	D	0.359	neutral	None	None	None	None	N
N/S	0.1352	likely_benign	0.1291	benign	-0.338	Destabilizing	0.826	D	0.4	neutral	N	0.497635111	None	None	N
N/T	0.2788	likely_benign	0.2648	benign	-0.147	Destabilizing	0.959	D	0.313	neutral	N	0.49069163	None	None	N
N/V	0.4561	ambiguous	0.4657	ambiguous	-0.035	Destabilizing	0.991	D	0.434	neutral	None	None	None	None	N
N/W	0.9466	likely_pathogenic	0.9469	pathogenic	-0.524	Destabilizing	0.999	D	0.564	neutral	None	None	None	None	N
N/Y	0.4032	ambiguous	0.4362	ambiguous	-0.266	Destabilizing	0.996	D	0.457	neutral	N	0.516116105	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.