TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18699	56320;56321;56322	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
N2AB	17058	51397;51398;51399	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
N2A	16131	48616;48617;48618	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
N2B	9634	29125;29126;29127	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
Novex-1	9759	29500;29501;29502	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
Novex-2	9826	29701;29702;29703	chr2:178599806;178599805;178599804	chr2:179464533;179464532;179464531
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-116
• Domain position: 12
• Structural Position: 24
• Q(SASA): 0.3491
• 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
G/E	rs1060500533	None	1.0	D	0.772	0.721	0.860385415557	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	2.62329E-04	0	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
G/A	0.3786	ambiguous	0.4129	ambiguous	-0.427	Destabilizing	1.0	D	0.682	prob.neutral	D	0.596430538	None	None	N
G/C	0.5388	ambiguous	0.5714	pathogenic	-0.922	Destabilizing	1.0	D	0.788	deleterious	None	None	None	None	N
G/D	0.2709	likely_benign	0.3244	benign	-1.08	Destabilizing	0.921	D	0.573	neutral	None	None	None	None	N
G/E	0.3942	ambiguous	0.4676	ambiguous	-1.246	Destabilizing	1.0	D	0.772	deleterious	D	0.591535438	None	None	N
G/F	0.8399	likely_pathogenic	0.8486	pathogenic	-1.253	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
G/H	0.6348	likely_pathogenic	0.6779	pathogenic	-0.645	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/I	0.8132	likely_pathogenic	0.8528	pathogenic	-0.572	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/K	0.5461	ambiguous	0.6462	pathogenic	-0.837	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
G/L	0.7771	likely_pathogenic	0.7929	pathogenic	-0.572	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
G/M	0.7515	likely_pathogenic	0.7703	pathogenic	-0.376	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
G/N	0.3271	likely_benign	0.3456	ambiguous	-0.562	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
G/P	0.9891	likely_pathogenic	0.9907	pathogenic	-0.492	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
G/Q	0.5268	ambiguous	0.5915	pathogenic	-0.935	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
G/R	0.5153	ambiguous	0.6142	pathogenic	-0.328	Destabilizing	1.0	D	0.805	deleterious	D	0.612883868	None	None	N
G/S	0.2557	likely_benign	0.2677	benign	-0.659	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
G/T	0.5125	ambiguous	0.5447	ambiguous	-0.773	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
G/V	0.7059	likely_pathogenic	0.7544	pathogenic	-0.492	Destabilizing	1.0	D	0.793	deleterious	D	0.622372258	None	None	N
G/W	0.7369	likely_pathogenic	0.7817	pathogenic	-1.372	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
G/Y	0.6828	likely_pathogenic	0.7211	pathogenic	-1.022	Destabilizing	1.0	D	0.804	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.