TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13739	41440;41441;41442	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
N2AB	12098	36517;36518;36519	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
N2A	11171	33736;33737;33738	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
N2B	4674	14245;14246;14247	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
Novex-1	4799	14620;14621;14622	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
Novex-2	4866	14821;14822;14823	chr2:178636512;178636511;178636510	chr2:179501239;179501238;179501237
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-87
• Domain position: 56
• Structural Position: 134
• Q(SASA): 0.3565
• 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	rs2060461606	None	1.0	N	0.743	0.316	0.330331372229	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs2060461606	None	1.0	N	0.743	0.316	0.330331372229	gnomAD-4.0.0	6.57488E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47089E-05	0	0
K/R	None	None	0.999	N	0.633	0.258	0.518641613453	gnomAD-4.0.0	1.59193E-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	0.965	likely_pathogenic	0.9772	pathogenic	-0.517	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/C	0.9921	likely_pathogenic	0.9932	pathogenic	-0.628	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
K/D	0.9806	likely_pathogenic	0.9879	pathogenic	0.199	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
K/E	0.9473	likely_pathogenic	0.96	pathogenic	0.249	Stabilizing	0.999	D	0.7	prob.neutral	N	0.501375552	None	None	N
K/F	0.9958	likely_pathogenic	0.9962	pathogenic	-0.616	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/G	0.964	likely_pathogenic	0.9729	pathogenic	-0.784	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/H	0.9241	likely_pathogenic	0.9281	pathogenic	-1.187	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/I	0.9752	likely_pathogenic	0.9787	pathogenic	0.132	Stabilizing	1.0	D	0.78	deleterious	N	0.503788754	None	None	N
K/L	0.9593	likely_pathogenic	0.962	pathogenic	0.132	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/M	0.9221	likely_pathogenic	0.9279	pathogenic	0.135	Stabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/N	0.9537	likely_pathogenic	0.9639	pathogenic	-0.106	Destabilizing	1.0	D	0.743	deleterious	N	0.504009105	None	None	N
K/P	0.9753	likely_pathogenic	0.9861	pathogenic	-0.055	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/Q	0.8356	likely_pathogenic	0.8455	pathogenic	-0.331	Destabilizing	1.0	D	0.741	deleterious	N	0.508220491	None	None	N
K/R	0.2752	likely_benign	0.2559	benign	-0.293	Destabilizing	0.999	D	0.633	neutral	N	0.491818601	None	None	N
K/S	0.9714	likely_pathogenic	0.9798	pathogenic	-0.832	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
K/T	0.9114	likely_pathogenic	0.9294	pathogenic	-0.601	Destabilizing	1.0	D	0.769	deleterious	N	0.501713739	None	None	N
K/V	0.9633	likely_pathogenic	0.972	pathogenic	-0.055	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/W	0.9918	likely_pathogenic	0.9931	pathogenic	-0.452	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/Y	0.9843	likely_pathogenic	0.9836	pathogenic	-0.117	Destabilizing	1.0	D	0.749	deleterious	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.