TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19019	57280;57281;57282	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
N2AB	17378	52357;52358;52359	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
N2A	16451	49576;49577;49578	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
N2B	9954	30085;30086;30087	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
Novex-1	10079	30460;30461;30462	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
Novex-2	10146	30661;30662;30663	chr2:178598562;178598561;178598560	chr2:179463289;179463288;179463287
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: Fn3-26
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.5793
• Predicted PPI site: I

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	None	None	0.117	N	0.542	0.11	0.19670166235	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	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	0.3358	likely_benign	0.2997	benign	0.05	Stabilizing	0.149	N	0.517	neutral	None	None	None	None	I
K/C	0.7547	likely_pathogenic	0.734	pathogenic	-0.125	Destabilizing	0.935	D	0.631	neutral	None	None	None	None	I
K/D	0.6427	likely_pathogenic	0.5732	pathogenic	0.055	Stabilizing	0.38	N	0.524	neutral	None	None	None	None	I
K/E	0.2576	likely_benign	0.206	benign	0.047	Stabilizing	0.062	N	0.509	neutral	N	0.428896947	None	None	I
K/F	0.8336	likely_pathogenic	0.8108	pathogenic	-0.244	Destabilizing	0.38	N	0.623	neutral	None	None	None	None	I
K/G	0.5484	ambiguous	0.5138	ambiguous	-0.125	Destabilizing	0.149	N	0.546	neutral	None	None	None	None	I
K/H	0.3947	ambiguous	0.3766	ambiguous	-0.414	Destabilizing	0.824	D	0.54	neutral	None	None	None	None	I
K/I	0.4298	ambiguous	0.3752	ambiguous	0.425	Stabilizing	0.188	N	0.615	neutral	N	0.508245952	None	None	I
K/L	0.4244	ambiguous	0.3882	ambiguous	0.425	Stabilizing	0.081	N	0.569	neutral	None	None	None	None	I
K/M	0.3405	ambiguous	0.2896	benign	0.289	Stabilizing	0.035	N	0.503	neutral	None	None	None	None	I
K/N	0.5549	ambiguous	0.4906	ambiguous	0.335	Stabilizing	0.317	N	0.461	neutral	N	0.495604729	None	None	I
K/P	0.4118	ambiguous	0.3714	ambiguous	0.327	Stabilizing	0.001	N	0.29	neutral	None	None	None	None	I
K/Q	0.1783	likely_benign	0.171	benign	0.129	Stabilizing	0.317	N	0.475	neutral	N	0.485291735	None	None	I
K/R	0.0707	likely_benign	0.0789	benign	0.071	Stabilizing	None	N	0.147	neutral	N	0.480059273	None	None	I
K/S	0.5123	ambiguous	0.4516	ambiguous	-0.142	Destabilizing	0.149	N	0.471	neutral	None	None	None	None	I
K/T	0.2631	likely_benign	0.2173	benign	-0.01	Destabilizing	0.117	N	0.542	neutral	N	0.477845688	None	None	I
K/V	0.3609	ambiguous	0.3111	benign	0.327	Stabilizing	0.081	N	0.537	neutral	None	None	None	None	I
K/W	0.7838	likely_pathogenic	0.8039	pathogenic	-0.27	Destabilizing	0.935	D	0.695	prob.neutral	None	None	None	None	I
K/Y	0.7184	likely_pathogenic	0.6944	pathogenic	0.1	Stabilizing	0.555	D	0.61	neutral	None	None	None	None	I

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.