TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26617	80074;80075;80076	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
N2AB	24976	75151;75152;75153	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
N2A	24049	72370;72371;72372	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
N2B	17552	52879;52880;52881	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
Novex-1	17677	53254;53255;53256	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
Novex-2	17744	53455;53456;53457	chr2:178566283;178566282;178566281	chr2:179431010;179431009;179431008
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-138
• Domain position: 24
• Structural Position: 38
• Q(SASA): 0.8288
• 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	None	None	0.046	N	0.229	0.151	0.247322355667	gnomAD-4.0.0	3.60103E-06	None	None	None	None	N	None	1.26695E-04	0	None	0	0	None	0	6.17284E-04	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
K/A	0.5093	ambiguous	0.5225	ambiguous	-0.063	Destabilizing	0.953	D	0.555	neutral	None	None	None	None	N
K/C	0.5874	likely_pathogenic	0.6298	pathogenic	-0.584	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
K/D	0.8604	likely_pathogenic	0.8651	pathogenic	-0.351	Destabilizing	0.993	D	0.65	neutral	None	None	None	None	N
K/E	0.437	ambiguous	0.4204	ambiguous	-0.352	Destabilizing	0.939	D	0.54	neutral	N	0.51412428	None	None	N
K/F	0.7919	likely_pathogenic	0.8021	pathogenic	-0.42	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
K/G	0.6457	likely_pathogenic	0.6791	pathogenic	-0.187	Destabilizing	0.993	D	0.523	neutral	None	None	None	None	N
K/H	0.2575	likely_benign	0.27	benign	-0.242	Destabilizing	0.998	D	0.664	neutral	None	None	None	None	N
K/I	0.4308	ambiguous	0.4372	ambiguous	0.185	Stabilizing	0.991	D	0.676	prob.neutral	N	0.502909995	None	None	N
K/L	0.48	ambiguous	0.494	ambiguous	0.185	Stabilizing	0.986	D	0.523	neutral	None	None	None	None	N
K/M	0.3597	ambiguous	0.3681	ambiguous	-0.279	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
K/N	0.6829	likely_pathogenic	0.6863	pathogenic	-0.149	Destabilizing	0.982	D	0.63	neutral	N	0.49306307	None	None	N
K/P	0.9689	likely_pathogenic	0.973	pathogenic	0.125	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	N
K/Q	0.1699	likely_benign	0.1732	benign	-0.246	Destabilizing	0.982	D	0.629	neutral	D	0.522765193	None	None	N
K/R	0.0642	likely_benign	0.0664	benign	-0.131	Destabilizing	0.046	N	0.229	neutral	N	0.454886762	None	None	N
K/S	0.5417	ambiguous	0.5553	ambiguous	-0.475	Destabilizing	0.953	D	0.588	neutral	None	None	None	None	N
K/T	0.2689	likely_benign	0.258	benign	-0.358	Destabilizing	0.991	D	0.609	neutral	N	0.471085579	None	None	N
K/V	0.4177	ambiguous	0.4188	ambiguous	0.125	Stabilizing	0.993	D	0.63	neutral	None	None	None	None	N
K/W	0.6505	likely_pathogenic	0.7091	pathogenic	-0.549	Destabilizing	0.999	D	0.712	prob.delet.	None	None	None	None	N
K/Y	0.6514	likely_pathogenic	0.6846	pathogenic	-0.196	Destabilizing	0.998	D	0.657	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.