TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14947	45064;45065;45066	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
N2AB	13306	40141;40142;40143	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
N2A	12379	37360;37361;37362	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
N2B	5882	17869;17870;17871	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
Novex-1	6007	18244;18245;18246	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
Novex-2	6074	18445;18446;18447	chr2:178622744;178622743;178622742	chr2:179487471;179487470;179487469
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-101
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.511
• 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/Q	rs1030725519	None	0.999	D	0.82	0.462	None	gnomAD-3.1.2	6.6E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	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	0.1963	likely_benign	0.1973	benign	-0.957	Destabilizing	0.996	D	0.702	prob.neutral	D	0.607874659	None	None	N
P/C	0.8496	likely_pathogenic	0.8186	pathogenic	-0.556	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
P/D	0.695	likely_pathogenic	0.7224	pathogenic	-0.288	Destabilizing	0.996	D	0.766	deleterious	None	None	None	None	N
P/E	0.4906	ambiguous	0.4827	ambiguous	-0.321	Destabilizing	0.998	D	0.777	deleterious	None	None	None	None	N
P/F	0.8382	likely_pathogenic	0.832	pathogenic	-0.766	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
P/G	0.5464	ambiguous	0.5565	ambiguous	-1.222	Destabilizing	0.994	D	0.707	prob.neutral	None	None	None	None	N
P/H	0.4285	ambiguous	0.4252	ambiguous	-0.745	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/I	0.6925	likely_pathogenic	0.7021	pathogenic	-0.361	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
P/K	0.5248	ambiguous	0.5313	ambiguous	-0.622	Destabilizing	0.998	D	0.769	deleterious	None	None	None	None	N
P/L	0.3364	likely_benign	0.3346	benign	-0.361	Destabilizing	0.999	D	0.802	deleterious	N	0.498920137	None	None	N
P/M	0.6594	likely_pathogenic	0.6528	pathogenic	-0.31	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
P/N	0.6032	likely_pathogenic	0.6322	pathogenic	-0.355	Destabilizing	0.833	D	0.408	neutral	None	None	None	None	N
P/Q	0.3309	likely_benign	0.325	benign	-0.517	Destabilizing	0.999	D	0.82	deleterious	D	0.574114939	None	None	N
P/R	0.3899	ambiguous	0.3853	ambiguous	-0.19	Destabilizing	0.999	D	0.793	deleterious	N	0.511607447	None	None	N
P/S	0.2841	likely_benign	0.2925	benign	-0.886	Destabilizing	0.998	D	0.749	deleterious	N	0.511912347	None	None	N
P/T	0.2923	likely_benign	0.2948	benign	-0.807	Destabilizing	0.998	D	0.772	deleterious	N	0.498393516	None	None	N
P/V	0.517	ambiguous	0.5248	ambiguous	-0.523	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/W	0.9204	likely_pathogenic	0.9209	pathogenic	-0.914	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/Y	0.7532	likely_pathogenic	0.7571	pathogenic	-0.599	Destabilizing	1.0	D	0.778	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.