TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7865	23818;23819;23820	chr2:178720049;178720048;178720047	chr2:179584776;179584775;179584774
N2AB	7548	22867;22868;22869	chr2:178720049;178720048;178720047	chr2:179584776;179584775;179584774
N2A	6621	20086;20087;20088	chr2:178720049;178720048;178720047	chr2:179584776;179584775;179584774
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-63
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.6959
• 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	rs746952741	-0.185	0.226	N	0.351	0.172	0.343560092441	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs746952741	-0.185	0.226	N	0.351	0.172	0.343560092441	gnomAD-4.0.0	2.7373E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59827E-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	0.6203	likely_pathogenic	0.606	pathogenic	-0.508	Destabilizing	0.998	D	0.654	neutral	None	None	None	None	N
K/C	0.8697	likely_pathogenic	0.861	pathogenic	-0.589	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
K/D	0.7554	likely_pathogenic	0.754	pathogenic	0.297	Stabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
K/E	0.2917	likely_benign	0.3008	benign	0.38	Stabilizing	0.985	D	0.608	neutral	N	0.49044213	None	None	N
K/F	0.8444	likely_pathogenic	0.8349	pathogenic	-0.379	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/G	0.7429	likely_pathogenic	0.7238	pathogenic	-0.827	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
K/H	0.3963	ambiguous	0.385	ambiguous	-1.123	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/I	0.4358	ambiguous	0.4112	ambiguous	0.292	Stabilizing	0.993	D	0.735	prob.delet.	D	0.523170624	None	None	N
K/L	0.4921	ambiguous	0.4859	ambiguous	0.292	Stabilizing	0.984	D	0.678	prob.neutral	None	None	None	None	N
K/M	0.3385	likely_benign	0.3317	benign	0.187	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/N	0.5196	ambiguous	0.5152	ambiguous	-0.184	Destabilizing	0.999	D	0.699	prob.neutral	D	0.532867543	None	None	N
K/P	0.8749	likely_pathogenic	0.8627	pathogenic	0.055	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/Q	0.2001	likely_benign	0.1965	benign	-0.32	Destabilizing	0.989	D	0.693	prob.neutral	N	0.485910274	None	None	N
K/R	0.0916	likely_benign	0.0894	benign	-0.351	Destabilizing	0.226	N	0.351	neutral	N	0.508721247	None	None	N
K/S	0.6145	likely_pathogenic	0.6049	pathogenic	-0.934	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
K/T	0.2828	likely_benign	0.2812	benign	-0.652	Destabilizing	0.998	D	0.743	deleterious	N	0.486999181	None	None	N
K/V	0.4725	ambiguous	0.4488	ambiguous	0.055	Stabilizing	0.988	D	0.739	prob.delet.	None	None	None	None	N
K/W	0.8254	likely_pathogenic	0.8284	pathogenic	-0.217	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
K/Y	0.704	likely_pathogenic	0.6915	pathogenic	0.095	Stabilizing	0.997	D	0.736	prob.delet.	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.