TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7245	21958;21959;21960	chr2:178723274;178723273;178723272	chr2:179588001;179588000;179587999
N2AB	6928	21007;21008;21009	chr2:178723274;178723273;178723272	chr2:179588001;179588000;179587999
N2A	6001	18226;18227;18228	chr2:178723274;178723273;178723272	chr2:179588001;179588000;179587999
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-57
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.375
• 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/T	None	None	0.001	N	0.222	0.094	0.177238962908	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	0.4085	ambiguous	0.424	ambiguous	-0.231	Destabilizing	0.116	N	0.321	neutral	None	None	None	None	N
K/C	0.7196	likely_pathogenic	0.7304	pathogenic	-0.268	Destabilizing	0.944	D	0.434	neutral	None	None	None	None	N
K/D	0.5266	ambiguous	0.5546	ambiguous	0.137	Stabilizing	0.241	N	0.327	neutral	None	None	None	None	N
K/E	0.1757	likely_benign	0.1824	benign	0.155	Stabilizing	0.001	N	0.173	neutral	N	0.435694342	None	None	N
K/F	0.772	likely_pathogenic	0.7853	pathogenic	-0.427	Destabilizing	0.818	D	0.387	neutral	None	None	None	None	N
K/G	0.4721	ambiguous	0.4891	ambiguous	-0.464	Destabilizing	0.388	N	0.382	neutral	None	None	None	None	N
K/H	0.2873	likely_benign	0.3042	benign	-0.892	Destabilizing	0.818	D	0.301	neutral	None	None	None	None	N
K/I	0.4333	ambiguous	0.452	ambiguous	0.313	Stabilizing	0.527	D	0.403	neutral	None	None	None	None	N
K/L	0.4374	ambiguous	0.4614	ambiguous	0.313	Stabilizing	0.241	N	0.415	neutral	None	None	None	None	N
K/M	0.2817	likely_benign	0.3011	benign	0.326	Stabilizing	0.928	D	0.295	neutral	N	0.513544624	None	None	N
K/N	0.3264	likely_benign	0.3419	ambiguous	0.143	Stabilizing	0.015	N	0.297	neutral	N	0.496265585	None	None	N
K/P	0.9208	likely_pathogenic	0.9149	pathogenic	0.161	Stabilizing	0.818	D	0.306	neutral	None	None	None	None	N
K/Q	0.1248	likely_benign	0.1322	benign	-0.089	Destabilizing	0.193	N	0.363	neutral	N	0.429232516	None	None	N
K/R	0.0852	likely_benign	0.0877	benign	-0.134	Destabilizing	0.001	N	0.349	neutral	N	0.498132454	None	None	N
K/S	0.3703	ambiguous	0.3852	ambiguous	-0.459	Destabilizing	0.241	N	0.299	neutral	None	None	None	None	N
K/T	0.2098	likely_benign	0.2254	benign	-0.276	Destabilizing	0.001	N	0.222	neutral	N	0.497785738	None	None	N
K/V	0.4051	ambiguous	0.4223	ambiguous	0.161	Stabilizing	0.241	N	0.399	neutral	None	None	None	None	N
K/W	0.7885	likely_pathogenic	0.7941	pathogenic	-0.349	Destabilizing	0.981	D	0.532	neutral	None	None	None	None	N
K/Y	0.5949	likely_pathogenic	0.6094	pathogenic	0.002	Stabilizing	0.818	D	0.377	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.