TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7579	22960;22961;22962	chr2:178721928;178721927;178721926	chr2:179586655;179586654;179586653
N2AB	7262	22009;22010;22011	chr2:178721928;178721927;178721926	chr2:179586655;179586654;179586653
N2A	6335	19228;19229;19230	chr2:178721928;178721927;178721926	chr2:179586655;179586654;179586653
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-60
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.5973
• 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/N	None	None	0.994	N	0.365	0.262	0.192905019026	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
K/R	rs2078428721	None	0.014	N	0.233	0.105	0.168933306366	gnomAD-4.0.0	1.59185E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85956E-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	0.5378	ambiguous	0.4991	ambiguous	-0.059	Destabilizing	0.971	D	0.449	neutral	None	None	None	None	N
K/C	0.9068	likely_pathogenic	0.9015	pathogenic	-0.55	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/D	0.8126	likely_pathogenic	0.7729	pathogenic	-0.273	Destabilizing	0.996	D	0.397	neutral	None	None	None	None	N
K/E	0.4316	ambiguous	0.3631	ambiguous	-0.295	Destabilizing	0.883	D	0.421	neutral	N	0.430638026	None	None	N
K/F	0.8748	likely_pathogenic	0.8654	pathogenic	-0.454	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
K/G	0.6976	likely_pathogenic	0.6802	pathogenic	-0.155	Destabilizing	0.985	D	0.421	neutral	None	None	None	None	N
K/H	0.5136	ambiguous	0.494	ambiguous	-0.244	Destabilizing	0.999	D	0.459	neutral	None	None	None	None	N
K/I	0.512	ambiguous	0.4913	ambiguous	0.11	Stabilizing	0.941	D	0.571	neutral	N	0.477487823	None	None	N
K/L	0.5177	ambiguous	0.5018	ambiguous	0.11	Stabilizing	0.666	D	0.429	neutral	None	None	None	None	N
K/M	0.4225	ambiguous	0.4077	ambiguous	-0.173	Destabilizing	0.997	D	0.468	neutral	None	None	None	None	N
K/N	0.663	likely_pathogenic	0.6134	pathogenic	-0.088	Destabilizing	0.994	D	0.365	neutral	N	0.453894915	None	None	N
K/P	0.6063	likely_pathogenic	0.5836	pathogenic	0.075	Stabilizing	0.195	N	0.302	neutral	None	None	None	None	N
K/Q	0.2571	likely_benign	0.2409	benign	-0.223	Destabilizing	0.915	D	0.399	neutral	N	0.483760435	None	None	N
K/R	0.093	likely_benign	0.0935	benign	-0.184	Destabilizing	0.014	N	0.233	neutral	N	0.464518526	None	None	N
K/S	0.628	likely_pathogenic	0.5948	pathogenic	-0.454	Destabilizing	0.985	D	0.39	neutral	None	None	None	None	N
K/T	0.3617	ambiguous	0.3421	ambiguous	-0.37	Destabilizing	0.982	D	0.399	neutral	N	0.486915383	None	None	N
K/V	0.5038	ambiguous	0.4843	ambiguous	0.075	Stabilizing	0.902	D	0.471	neutral	None	None	None	None	N
K/W	0.865	likely_pathogenic	0.8666	pathogenic	-0.56	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
K/Y	0.8009	likely_pathogenic	0.7918	pathogenic	-0.212	Destabilizing	0.971	D	0.534	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.