TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17850	53773;53774;53775	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
N2AB	16209	48850;48851;48852	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
N2A	15282	46069;46070;46071	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
N2B	8785	26578;26579;26580	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
Novex-1	8910	26953;26954;26955	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
Novex-2	8977	27154;27155;27156	chr2:178607054;178607053;178607052	chr2:179471781;179471780;179471779
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: Fn3-17
• Domain position: 87
• Structural Position: 122
• Q(SASA): 0.2868
• 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	rs780284047	-0.399	0.799	N	0.559	0.272	0.316494231283	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
E/A	rs780284047	-0.399	0.799	N	0.559	0.272	0.316494231283	gnomAD-4.0.0	2.05544E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8002E-06	0	1.65942E-05

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	0.4957	ambiguous	0.4694	ambiguous	-0.542	Destabilizing	0.799	D	0.559	neutral	N	0.514475704	None	None	N
E/C	0.9369	likely_pathogenic	0.9377	pathogenic	-0.374	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
E/D	0.1908	likely_benign	0.1977	benign	-1.027	Destabilizing	0.002	N	0.161	neutral	N	0.473437158	None	None	N
E/F	0.9219	likely_pathogenic	0.9204	pathogenic	0.322	Stabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
E/G	0.6978	likely_pathogenic	0.648	pathogenic	-0.952	Destabilizing	0.799	D	0.619	neutral	N	0.478406223	None	None	N
E/H	0.8422	likely_pathogenic	0.8455	pathogenic	0.158	Stabilizing	0.991	D	0.651	prob.neutral	None	None	None	None	N
E/I	0.6293	likely_pathogenic	0.6539	pathogenic	0.591	Stabilizing	0.974	D	0.796	deleterious	None	None	None	None	N
E/K	0.6742	likely_pathogenic	0.6716	pathogenic	-0.522	Destabilizing	0.799	D	0.469	neutral	N	0.468998474	None	None	N
E/L	0.7503	likely_pathogenic	0.7431	pathogenic	0.591	Stabilizing	0.974	D	0.735	deleterious	None	None	None	None	N
E/M	0.7466	likely_pathogenic	0.738	pathogenic	0.905	Stabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
E/N	0.5876	likely_pathogenic	0.5919	pathogenic	-1.139	Destabilizing	0.725	D	0.519	neutral	None	None	None	None	N
E/P	0.9032	likely_pathogenic	0.9274	pathogenic	0.235	Stabilizing	0.974	D	0.63	neutral	None	None	None	None	N
E/Q	0.4948	ambiguous	0.4765	ambiguous	-0.939	Destabilizing	0.89	D	0.555	neutral	N	0.465226265	None	None	N
E/R	0.7933	likely_pathogenic	0.8012	pathogenic	-0.157	Destabilizing	0.974	D	0.547	neutral	None	None	None	None	N
E/S	0.5249	ambiguous	0.495	ambiguous	-1.477	Destabilizing	0.841	D	0.442	neutral	None	None	None	None	N
E/T	0.4885	ambiguous	0.4808	ambiguous	-1.126	Destabilizing	0.915	D	0.636	neutral	None	None	None	None	N
E/V	0.4236	ambiguous	0.4415	ambiguous	0.235	Stabilizing	0.966	D	0.635	neutral	N	0.469505453	None	None	N
E/W	0.97	likely_pathogenic	0.9719	pathogenic	0.58	Stabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
E/Y	0.8737	likely_pathogenic	0.8784	pathogenic	0.594	Stabilizing	0.991	D	0.795	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.