TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5932	18019;18020;18021	chr2:178730739;178730738;178730737	chr2:179595466;179595465;179595464
N2AB	5615	17068;17069;17070	chr2:178730739;178730738;178730737	chr2:179595466;179595465;179595464
N2A	4688	14287;14288;14289	chr2:178730739;178730738;178730737	chr2:179595466;179595465;179595464
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-43
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.6828
• 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	rs879062650	None	0.998	N	0.553	0.41	None	gnomAD-4.0.0	1.59791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87394E-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	0.4806	ambiguous	0.5182	ambiguous	-0.169	Destabilizing	0.996	D	0.532	neutral	None	None	None	None	N
K/C	0.8367	likely_pathogenic	0.8481	pathogenic	-0.377	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
K/D	0.8463	likely_pathogenic	0.8772	pathogenic	0.322	Stabilizing	1.0	D	0.584	neutral	None	None	None	None	N
K/E	0.2668	likely_benign	0.3025	benign	0.359	Stabilizing	0.998	D	0.561	neutral	N	0.406544871	None	None	N
K/F	0.9102	likely_pathogenic	0.9262	pathogenic	-0.214	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
K/G	0.7181	likely_pathogenic	0.7716	pathogenic	-0.421	Destabilizing	1.0	D	0.534	neutral	None	None	None	None	N
K/H	0.5173	ambiguous	0.5388	ambiguous	-0.682	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	N
K/I	0.4723	ambiguous	0.5163	ambiguous	0.43	Stabilizing	0.994	D	0.611	neutral	N	0.427059003	None	None	N
K/L	0.5138	ambiguous	0.5275	ambiguous	0.43	Stabilizing	0.269	N	0.426	neutral	None	None	None	None	N
K/M	0.3629	ambiguous	0.3809	ambiguous	0.24	Stabilizing	0.998	D	0.575	neutral	None	None	None	None	N
K/N	0.6914	likely_pathogenic	0.733	pathogenic	0.093	Stabilizing	0.999	D	0.617	neutral	N	0.499479248	None	None	N
K/P	0.8155	likely_pathogenic	0.8782	pathogenic	0.26	Stabilizing	1.0	D	0.57	neutral	None	None	None	None	N
K/Q	0.1716	likely_benign	0.1888	benign	-0.077	Destabilizing	0.999	D	0.629	neutral	N	0.468156264	None	None	N
K/R	0.0962	likely_benign	0.0973	benign	-0.132	Destabilizing	0.998	D	0.539	neutral	N	0.46690547	None	None	N
K/S	0.5922	likely_pathogenic	0.6516	pathogenic	-0.541	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
K/T	0.31	likely_benign	0.3586	ambiguous	-0.333	Destabilizing	0.998	D	0.553	neutral	N	0.460267499	None	None	N
K/V	0.4463	ambiguous	0.4912	ambiguous	0.26	Stabilizing	0.983	D	0.503	neutral	None	None	None	None	N
K/W	0.9002	likely_pathogenic	0.9141	pathogenic	-0.133	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/Y	0.8176	likely_pathogenic	0.8372	pathogenic	0.198	Stabilizing	1.0	D	0.635	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.