TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30373	91342;91343;91344	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
N2AB	28732	86419;86420;86421	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
N2A	27805	83638;83639;83640	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
N2B	21308	64147;64148;64149	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
Novex-1	21433	64522;64523;64524	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
Novex-2	21500	64723;64724;64725	chr2:178551783;178551782;178551781	chr2:179416510;179416509;179416508
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: Fn3-109
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.5782
• 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/Q	None	None	0.468	N	0.708	0.147	0.181679512989	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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	0.568	likely_pathogenic	0.5582	ambiguous	-0.344	Destabilizing	0.399	N	0.596	neutral	None	None	None	None	N
K/C	0.7276	likely_pathogenic	0.7387	pathogenic	-0.393	Destabilizing	0.982	D	0.707	prob.neutral	None	None	None	None	N
K/D	0.8445	likely_pathogenic	0.839	pathogenic	-0.144	Destabilizing	0.7	D	0.764	deleterious	None	None	None	None	N
K/E	0.4389	ambiguous	0.4281	ambiguous	-0.062	Destabilizing	0.201	N	0.553	neutral	N	0.480515059	None	None	N
K/F	0.874	likely_pathogenic	0.8747	pathogenic	-0.098	Destabilizing	0.947	D	0.711	prob.delet.	None	None	None	None	N
K/G	0.6877	likely_pathogenic	0.6968	pathogenic	-0.687	Destabilizing	0.7	D	0.665	neutral	None	None	None	None	N
K/H	0.3965	ambiguous	0.4129	ambiguous	-1.079	Destabilizing	0.947	D	0.754	deleterious	None	None	None	None	N
K/I	0.5002	ambiguous	0.4993	ambiguous	0.529	Stabilizing	0.781	D	0.73	prob.delet.	N	0.510688825	None	None	N
K/L	0.4585	ambiguous	0.4604	ambiguous	0.529	Stabilizing	0.7	D	0.665	neutral	None	None	None	None	N
K/M	0.3498	ambiguous	0.3463	ambiguous	0.387	Stabilizing	0.982	D	0.746	deleterious	None	None	None	None	N
K/N	0.6826	likely_pathogenic	0.6734	pathogenic	-0.329	Destabilizing	0.638	D	0.709	prob.delet.	N	0.513689058	None	None	N
K/P	0.6722	likely_pathogenic	0.6518	pathogenic	0.269	Stabilizing	0.826	D	0.77	deleterious	None	None	None	None	N
K/Q	0.2106	likely_benign	0.209	benign	-0.429	Destabilizing	0.468	N	0.708	prob.delet.	N	0.499605039	None	None	N
K/R	0.0704	likely_benign	0.073	benign	-0.586	Destabilizing	0.002	N	0.301	neutral	N	0.420682896	None	None	N
K/S	0.7109	likely_pathogenic	0.7108	pathogenic	-0.902	Destabilizing	0.399	N	0.631	neutral	None	None	None	None	N
K/T	0.3593	ambiguous	0.3625	ambiguous	-0.63	Destabilizing	0.638	D	0.745	deleterious	N	0.473861233	None	None	N
K/V	0.4661	ambiguous	0.4757	ambiguous	0.269	Stabilizing	0.7	D	0.728	prob.delet.	None	None	None	None	N
K/W	0.7544	likely_pathogenic	0.788	pathogenic	-0.014	Destabilizing	0.982	D	0.711	prob.delet.	None	None	None	None	N
K/Y	0.7298	likely_pathogenic	0.7362	pathogenic	0.276	Stabilizing	0.826	D	0.724	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.