TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32451	97576;97577;97578	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
N2AB	30810	92653;92654;92655	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
N2A	29883	89872;89873;89874	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
N2B	23386	70381;70382;70383	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
Novex-1	23511	70756;70757;70758	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
Novex-2	23578	70957;70958;70959	chr2:178542405;178542404;178542403	chr2:179407132;179407131;179407130
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-124
• Domain position: 53
• Structural Position: 69
• Q(SASA): 0.1824
• 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
S/C	None	None	1.0	N	0.806	0.419	0.457377140028	gnomAD-4.0.0	1.5915E-06	None	None	None	None	N	None	0	2.28666E-05	None	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
S/A	0.1636	likely_benign	0.1461	benign	-0.638	Destabilizing	0.997	D	0.419	neutral	N	0.470863787	None	None	N
S/C	0.1718	likely_benign	0.1445	benign	-0.421	Destabilizing	1.0	D	0.806	deleterious	N	0.485539928	None	None	N
S/D	0.9567	likely_pathogenic	0.9567	pathogenic	0.225	Stabilizing	0.999	D	0.551	neutral	None	None	None	None	N
S/E	0.9667	likely_pathogenic	0.9673	pathogenic	0.293	Stabilizing	0.999	D	0.537	neutral	None	None	None	None	N
S/F	0.812	likely_pathogenic	0.7832	pathogenic	-0.842	Destabilizing	1.0	D	0.822	deleterious	N	0.499249637	None	None	N
S/G	0.3291	likely_benign	0.2748	benign	-0.929	Destabilizing	0.999	D	0.496	neutral	None	None	None	None	N
S/H	0.875	likely_pathogenic	0.8693	pathogenic	-1.244	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
S/I	0.7299	likely_pathogenic	0.7193	pathogenic	0.041	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/K	0.9891	likely_pathogenic	0.9897	pathogenic	-0.14	Destabilizing	0.999	D	0.543	neutral	None	None	None	None	N
S/L	0.3679	ambiguous	0.3233	benign	0.041	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
S/M	0.5139	ambiguous	0.472	ambiguous	-0.016	Destabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
S/N	0.6513	likely_pathogenic	0.6029	pathogenic	-0.38	Destabilizing	0.999	D	0.524	neutral	None	None	None	None	N
S/P	0.9737	likely_pathogenic	0.9783	pathogenic	-0.15	Destabilizing	1.0	D	0.819	deleterious	N	0.482386376	None	None	N
S/Q	0.917	likely_pathogenic	0.9176	pathogenic	-0.32	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
S/R	0.9787	likely_pathogenic	0.9792	pathogenic	-0.264	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
S/T	0.2236	likely_benign	0.2056	benign	-0.354	Destabilizing	0.999	D	0.462	neutral	N	0.502663987	None	None	N
S/V	0.5926	likely_pathogenic	0.5858	pathogenic	-0.15	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
S/W	0.8524	likely_pathogenic	0.8423	pathogenic	-0.884	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
S/Y	0.7406	likely_pathogenic	0.7245	pathogenic	-0.518	Destabilizing	1.0	D	0.825	deleterious	N	0.471790539	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.