TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19027	57304;57305;57306	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
N2AB	17386	52381;52382;52383	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
N2A	16459	49600;49601;49602	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
N2B	9962	30109;30110;30111	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
Novex-1	10087	30484;30485;30486	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
Novex-2	10154	30685;30686;30687	chr2:178598538;178598537;178598536	chr2:179463265;179463264;179463263
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-26
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1756
• 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
Y/C	rs1275283475	-0.986	0.999	N	0.761	0.393	0.489036454283	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.43E-05	None	0	0	0
Y/C	rs1275283475	-0.986	0.999	N	0.761	0.393	0.489036454283	gnomAD-4.0.0	1.60327E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46593E-05	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
Y/A	0.7019	likely_pathogenic	0.7352	pathogenic	-2.335	Highly Destabilizing	0.976	D	0.71	prob.delet.	None	None	None	None	N
Y/C	0.1414	likely_benign	0.1581	benign	-1.032	Destabilizing	0.999	D	0.761	deleterious	N	0.478466491	None	None	N
Y/D	0.8776	likely_pathogenic	0.881	pathogenic	-3.146	Highly Destabilizing	0.997	D	0.8	deleterious	N	0.513602272	None	None	N
Y/E	0.8974	likely_pathogenic	0.9107	pathogenic	-2.921	Highly Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
Y/F	0.0596	likely_benign	0.0791	benign	-0.811	Destabilizing	0.046	N	0.313	neutral	N	0.490473842	None	None	N
Y/G	0.7589	likely_pathogenic	0.743	pathogenic	-2.747	Highly Destabilizing	0.993	D	0.761	deleterious	None	None	None	None	N
Y/H	0.3001	likely_benign	0.301	benign	-1.819	Destabilizing	0.997	D	0.734	prob.delet.	D	0.524106413	None	None	N
Y/I	0.4424	ambiguous	0.5285	ambiguous	-0.969	Destabilizing	0.973	D	0.703	prob.neutral	None	None	None	None	N
Y/K	0.7217	likely_pathogenic	0.7314	pathogenic	-1.827	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
Y/L	0.5603	ambiguous	0.5897	pathogenic	-0.969	Destabilizing	0.91	D	0.665	neutral	None	None	None	None	N
Y/M	0.5274	ambiguous	0.5712	pathogenic	-0.695	Destabilizing	0.998	D	0.73	prob.delet.	None	None	None	None	N
Y/N	0.5946	likely_pathogenic	0.5652	pathogenic	-2.757	Highly Destabilizing	0.997	D	0.767	deleterious	N	0.502245967	None	None	N
Y/P	0.9951	likely_pathogenic	0.9957	pathogenic	-1.439	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
Y/Q	0.6901	likely_pathogenic	0.7017	pathogenic	-2.398	Highly Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
Y/R	0.605	likely_pathogenic	0.6265	pathogenic	-1.942	Destabilizing	0.998	D	0.771	deleterious	None	None	None	None	N
Y/S	0.5609	ambiguous	0.5639	ambiguous	-2.964	Highly Destabilizing	0.991	D	0.739	prob.delet.	N	0.488743046	None	None	N
Y/T	0.7211	likely_pathogenic	0.7435	pathogenic	-2.609	Highly Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
Y/V	0.3709	ambiguous	0.4405	ambiguous	-1.439	Destabilizing	0.953	D	0.693	prob.neutral	None	None	None	None	N
Y/W	0.3316	likely_benign	0.368	ambiguous	-0.224	Destabilizing	0.999	D	0.73	prob.delet.	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.