TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31558	94897;94898;94899	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
N2AB	29917	89974;89975;89976	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
N2A	28990	87193;87194;87195	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
N2B	22493	67702;67703;67704	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
Novex-1	22618	68077;68078;68079	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
Novex-2	22685	68278;68279;68280	chr2:178546756;178546755;178546754	chr2:179411483;179411482;179411481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-118
• Domain position: 53
• Structural Position: 67
• Q(SASA): 0.345
• 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
K/N	None	None	1.0	N	0.726	0.368	0.282179105231	gnomAD-4.0.0	6.84212E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65662E-05

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
K/A	0.9852	likely_pathogenic	0.9768	pathogenic	-0.594	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/C	0.989	likely_pathogenic	0.9863	pathogenic	-0.479	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.9975	likely_pathogenic	0.9961	pathogenic	-0.127	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.9905	likely_pathogenic	0.9825	pathogenic	0.003	Stabilizing	0.999	D	0.571	neutral	N	0.515246496	None	None	N
K/F	0.9967	likely_pathogenic	0.996	pathogenic	-0.125	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/G	0.9929	likely_pathogenic	0.9901	pathogenic	-0.981	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/H	0.9176	likely_pathogenic	0.8923	pathogenic	-1.27	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
K/I	0.9784	likely_pathogenic	0.97	pathogenic	0.419	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/L	0.9535	likely_pathogenic	0.9413	pathogenic	0.419	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/M	0.9608	likely_pathogenic	0.9475	pathogenic	0.214	Stabilizing	1.0	D	0.741	deleterious	N	0.49377868	None	None	N
K/N	0.9938	likely_pathogenic	0.9897	pathogenic	-0.49	Destabilizing	1.0	D	0.726	prob.delet.	N	0.487182088	None	None	N
K/P	0.953	likely_pathogenic	0.9246	pathogenic	0.111	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
K/Q	0.8625	likely_pathogenic	0.7972	pathogenic	-0.482	Destabilizing	1.0	D	0.708	prob.delet.	D	0.522828616	None	None	N
K/R	0.1697	likely_benign	0.1498	benign	-0.675	Destabilizing	0.999	D	0.545	neutral	N	0.465185822	None	None	N
K/S	0.9929	likely_pathogenic	0.989	pathogenic	-1.1	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	N
K/T	0.9695	likely_pathogenic	0.9536	pathogenic	-0.759	Destabilizing	1.0	D	0.767	deleterious	N	0.497412883	None	None	N
K/V	0.9715	likely_pathogenic	0.9612	pathogenic	0.111	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/W	0.9949	likely_pathogenic	0.9939	pathogenic	-0.028	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/Y	0.9872	likely_pathogenic	0.9848	pathogenic	0.226	Stabilizing	1.0	D	0.767	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.