TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19289	58090;58091;58092	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
N2AB	17648	53167;53168;53169	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
N2A	16721	50386;50387;50388	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
N2B	10224	30895;30896;30897	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
Novex-1	10349	31270;31271;31272	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
Novex-2	10416	31471;31472;31473	chr2:178594629;178594628;178594627	chr2:179459356;179459355;179459354
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-28
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.2562
• 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
E/A	None	None	0.999	N	0.682	0.363	0.59128977468	gnomAD-4.0.0	1.6007E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87581E-06	0	0
E/K	rs1031046164	None	0.999	D	0.573	0.385	0.573099714865	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs1031046164	None	0.999	D	0.573	0.385	0.573099714865	gnomAD-4.0.0	6.57652E-06	None	None	None	None	N	None	2.41359E-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
E/A	0.3952	ambiguous	0.3688	ambiguous	-0.776	Destabilizing	0.999	D	0.682	prob.neutral	N	0.502493416	None	None	N
E/C	0.9411	likely_pathogenic	0.9296	pathogenic	-0.533	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/D	0.5119	ambiguous	0.4838	ambiguous	-1.124	Destabilizing	0.999	D	0.471	neutral	N	0.504090926	None	None	N
E/F	0.9447	likely_pathogenic	0.9347	pathogenic	-0.423	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
E/G	0.4695	ambiguous	0.4232	ambiguous	-1.117	Destabilizing	1.0	D	0.726	prob.delet.	N	0.463647026	None	None	N
E/H	0.8838	likely_pathogenic	0.8673	pathogenic	-0.841	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
E/I	0.5686	likely_pathogenic	0.5759	pathogenic	0.146	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/K	0.4668	ambiguous	0.4391	ambiguous	-0.973	Destabilizing	0.999	D	0.573	neutral	D	0.524060767	None	None	N
E/L	0.6974	likely_pathogenic	0.7028	pathogenic	0.146	Stabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/M	0.6812	likely_pathogenic	0.6818	pathogenic	0.559	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/N	0.6948	likely_pathogenic	0.6747	pathogenic	-1.221	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.9799	likely_pathogenic	0.9785	pathogenic	-0.14	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
E/Q	0.3135	likely_benign	0.3067	benign	-1.082	Destabilizing	1.0	D	0.613	neutral	N	0.477749687	None	None	N
E/R	0.6201	likely_pathogenic	0.5813	pathogenic	-0.735	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/S	0.5089	ambiguous	0.4924	ambiguous	-1.525	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
E/T	0.4556	ambiguous	0.465	ambiguous	-1.26	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/V	0.3697	ambiguous	0.3868	ambiguous	-0.14	Destabilizing	1.0	D	0.788	deleterious	N	0.50534172	None	None	N
E/W	0.983	likely_pathogenic	0.977	pathogenic	-0.307	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/Y	0.9295	likely_pathogenic	0.9103	pathogenic	-0.252	Destabilizing	1.0	D	0.806	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.