TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21959	66100;66101;66102	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
N2AB	20318	61177;61178;61179	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
N2A	19391	58396;58397;58398	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
N2B	12894	38905;38906;38907	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
Novex-1	13019	39280;39281;39282	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
Novex-2	13086	39481;39482;39483	chr2:178582581;178582580;178582579	chr2:179447308;179447307;179447306
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-47
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2507
• 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
P/L	None	None	1.0	D	0.869	0.469	0.657373984822	gnomAD-4.0.0	6.87087E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02582E-07	0	0
P/R	None	None	1.0	N	0.893	0.477	0.486851695374	gnomAD-4.0.0	1.37417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80516E-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
P/A	0.2058	likely_benign	0.1532	benign	-1.565	Destabilizing	1.0	D	0.817	deleterious	N	0.501949124	None	None	N
P/C	0.8044	likely_pathogenic	0.7039	pathogenic	-0.987	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/D	0.9552	likely_pathogenic	0.934	pathogenic	-1.887	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/E	0.7859	likely_pathogenic	0.6977	pathogenic	-1.916	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/F	0.8624	likely_pathogenic	0.7911	pathogenic	-1.354	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
P/G	0.8339	likely_pathogenic	0.7498	pathogenic	-1.85	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/H	0.6681	likely_pathogenic	0.5491	ambiguous	-1.433	Destabilizing	1.0	D	0.874	deleterious	D	0.530484624	None	None	N
P/I	0.646	likely_pathogenic	0.5216	ambiguous	-0.879	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
P/K	0.62	likely_pathogenic	0.4859	ambiguous	-1.265	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/L	0.4308	ambiguous	0.3116	benign	-0.879	Destabilizing	1.0	D	0.869	deleterious	D	0.530231134	None	None	N
P/M	0.6614	likely_pathogenic	0.5436	ambiguous	-0.597	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/N	0.8779	likely_pathogenic	0.8237	pathogenic	-1.027	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Q	0.5142	ambiguous	0.3943	ambiguous	-1.286	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
P/R	0.5159	ambiguous	0.379	ambiguous	-0.688	Destabilizing	1.0	D	0.893	deleterious	N	0.506086492	None	None	N
P/S	0.5373	ambiguous	0.4062	ambiguous	-1.441	Destabilizing	1.0	D	0.82	deleterious	N	0.482613412	None	None	N
P/T	0.5247	ambiguous	0.3801	ambiguous	-1.379	Destabilizing	1.0	D	0.821	deleterious	D	0.522976206	None	None	N
P/V	0.5225	ambiguous	0.4021	ambiguous	-1.075	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/W	0.962	likely_pathogenic	0.9367	pathogenic	-1.531	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/Y	0.8804	likely_pathogenic	0.8109	pathogenic	-1.262	Destabilizing	1.0	D	0.907	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.