TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3989	12190;12191;12192	chr2:178741268;178741267;178741266	chr2:179605995;179605994;179605993
N2AB	3672	11239;11240;11241	chr2:178741268;178741267;178741266	chr2:179605995;179605994;179605993
N2A	None	None	chr2:None	chr2:None
N2B	3626	11101;11102;11103	chr2:178741268;178741267;178741266	chr2:179605995;179605994;179605993
Novex-1	3751	11476;11477;11478	chr2:178741268;178741267;178741266	chr2:179605995;179605994;179605993
Novex-2	3818	11677;11678;11679	chr2:178741268;178741267;178741266	chr2:179605995;179605994;179605993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-28
• Domain position: 52
• Structural Position: 128
• Q(SASA): 0.2874
• 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	0.001	N	0.109	0.159	None	gnomAD-4.0.0	1.20032E-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	0.3393	likely_benign	0.3172	benign	-0.442	Destabilizing	0.116	N	0.336	neutral	None	None	None	None	N
N/C	0.3539	ambiguous	0.3216	benign	0.468	Stabilizing	0.944	D	0.413	neutral	None	None	None	None	N
N/D	0.1557	likely_benign	0.1423	benign	-0.233	Destabilizing	0.09	N	0.313	neutral	N	0.500291879	None	None	N
N/E	0.4008	ambiguous	0.3787	ambiguous	-0.249	Destabilizing	0.116	N	0.311	neutral	None	None	None	None	N
N/F	0.5485	ambiguous	0.5155	ambiguous	-0.708	Destabilizing	0.69	D	0.445	neutral	None	None	None	None	N
N/G	0.4112	ambiguous	0.3886	ambiguous	-0.657	Destabilizing	0.116	N	0.277	neutral	None	None	None	None	N
N/H	0.0875	likely_benign	0.0781	benign	-0.758	Destabilizing	0.001	N	0.107	neutral	D	0.543393912	None	None	N
N/I	0.256	likely_benign	0.2491	benign	0.048	Stabilizing	0.627	D	0.459	neutral	D	0.618071929	None	None	N
N/K	0.3194	likely_benign	0.3027	benign	-0.009	Destabilizing	0.001	N	0.114	neutral	N	0.503534856	None	None	N
N/L	0.2487	likely_benign	0.237	benign	0.048	Stabilizing	0.388	N	0.376	neutral	None	None	None	None	N
N/M	0.4137	ambiguous	0.4007	ambiguous	0.637	Stabilizing	0.818	D	0.368	neutral	None	None	None	None	N
N/P	0.7554	likely_pathogenic	0.7313	pathogenic	-0.088	Destabilizing	0.69	D	0.423	neutral	None	None	None	None	N
N/Q	0.3566	ambiguous	0.3429	ambiguous	-0.494	Destabilizing	0.008	N	0.171	neutral	None	None	None	None	N
N/R	0.3646	ambiguous	0.3361	benign	0.051	Stabilizing	0.241	N	0.264	neutral	None	None	None	None	N
N/S	0.107	likely_benign	0.1024	benign	-0.236	Destabilizing	0.001	N	0.109	neutral	N	0.508367426	None	None	N
N/T	0.1818	likely_benign	0.1765	benign	-0.103	Destabilizing	0.193	N	0.263	neutral	N	0.505965516	None	None	N
N/V	0.3434	ambiguous	0.3228	benign	-0.088	Destabilizing	0.388	N	0.4	neutral	None	None	None	None	N
N/W	0.82	likely_pathogenic	0.7784	pathogenic	-0.644	Destabilizing	0.981	D	0.445	neutral	None	None	None	None	N
N/Y	0.1724	likely_benign	0.1569	benign	-0.401	Destabilizing	0.457	N	0.42	neutral	N	0.514705971	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.