TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22291	67096;67097;67098	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
N2AB	20650	62173;62174;62175	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
N2A	19723	59392;59393;59394	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
N2B	13226	39901;39902;39903	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
Novex-1	13351	40276;40277;40278	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
Novex-2	13418	40477;40478;40479	chr2:178580508;178580507;178580506	chr2:179445235;179445234;179445233
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-126
• Domain position: 27
• Structural Position: 44
• Q(SASA): 0.2194
• Predicted PPI site: I

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/T	None	None	1.0	D	0.807	0.729	0.629339664297	gnomAD-4.0.0	3.18653E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72295E-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	0.7852	likely_pathogenic	0.7707	pathogenic	-1.625	Destabilizing	1.0	D	0.785	deleterious	D	0.525839583	None	None	I
P/C	0.9745	likely_pathogenic	0.9742	pathogenic	-1.211	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
P/D	0.9994	likely_pathogenic	0.9993	pathogenic	-1.465	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/E	0.9979	likely_pathogenic	0.9976	pathogenic	-1.454	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
P/F	0.9991	likely_pathogenic	0.9988	pathogenic	-1.323	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/G	0.9879	likely_pathogenic	0.9869	pathogenic	-1.957	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
P/H	0.9971	likely_pathogenic	0.9965	pathogenic	-1.579	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
P/I	0.9838	likely_pathogenic	0.9805	pathogenic	-0.803	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
P/K	0.9981	likely_pathogenic	0.9979	pathogenic	-1.283	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
P/L	0.955	likely_pathogenic	0.9455	pathogenic	-0.803	Destabilizing	1.0	D	0.782	deleterious	D	0.558334656	None	None	I
P/M	0.9917	likely_pathogenic	0.9907	pathogenic	-0.67	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/N	0.9989	likely_pathogenic	0.9988	pathogenic	-1.087	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
P/Q	0.9936	likely_pathogenic	0.9925	pathogenic	-1.251	Destabilizing	1.0	D	0.811	deleterious	D	0.562897467	None	None	I
P/R	0.9939	likely_pathogenic	0.9932	pathogenic	-0.836	Destabilizing	1.0	D	0.807	deleterious	D	0.562897467	None	None	I
P/S	0.9783	likely_pathogenic	0.9755	pathogenic	-1.639	Destabilizing	1.0	D	0.809	deleterious	D	0.562390488	None	None	I
P/T	0.9698	likely_pathogenic	0.9663	pathogenic	-1.515	Destabilizing	1.0	D	0.807	deleterious	D	0.562390488	None	None	I
P/V	0.9445	likely_pathogenic	0.9363	pathogenic	-1.043	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
P/W	0.9998	likely_pathogenic	0.9997	pathogenic	-1.515	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
P/Y	0.9992	likely_pathogenic	0.999	pathogenic	-1.215	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I

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.