TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22683	68272;68273;68274	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
N2AB	21042	63349;63350;63351	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
N2A	20115	60568;60569;60570	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
N2B	13618	41077;41078;41079	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
Novex-1	13743	41452;41453;41454	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
Novex-2	13810	41653;41654;41655	chr2:178578983;178578982;178578981	chr2:179443710;179443709;179443708
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: Fn3-52
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.2177
• 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/E	None	None	0.999	N	0.727	0.492	0.4018988957	gnomAD-4.0.0	2.73766E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59862E-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
K/A	0.9739	likely_pathogenic	0.9697	pathogenic	-1.339	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
K/C	0.9327	likely_pathogenic	0.9238	pathogenic	-1.272	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
K/D	0.9974	likely_pathogenic	0.9972	pathogenic	-1.587	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
K/E	0.9382	likely_pathogenic	0.9254	pathogenic	-1.27	Destabilizing	0.999	D	0.727	prob.delet.	N	0.49919673	None	None	N
K/F	0.9829	likely_pathogenic	0.9771	pathogenic	-0.664	Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
K/G	0.9798	likely_pathogenic	0.9778	pathogenic	-1.835	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/H	0.8431	likely_pathogenic	0.8275	pathogenic	-1.649	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/I	0.9163	likely_pathogenic	0.8937	pathogenic	0.073	Stabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
K/L	0.8773	likely_pathogenic	0.8533	pathogenic	0.073	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/M	0.6777	likely_pathogenic	0.6283	pathogenic	-0.287	Destabilizing	1.0	D	0.826	deleterious	N	0.512939696	None	None	N
K/N	0.9859	likely_pathogenic	0.9837	pathogenic	-1.579	Destabilizing	1.0	D	0.837	deleterious	N	0.517300985	None	None	N
K/P	0.9995	likely_pathogenic	0.9995	pathogenic	-0.377	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
K/Q	0.5759	likely_pathogenic	0.5207	ambiguous	-1.203	Destabilizing	1.0	D	0.841	deleterious	D	0.523079332	None	None	N
K/R	0.1674	likely_benign	0.1619	benign	-0.645	Destabilizing	0.999	D	0.72	prob.delet.	N	0.469591564	None	None	N
K/S	0.9829	likely_pathogenic	0.9797	pathogenic	-2.158	Highly Destabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
K/T	0.929	likely_pathogenic	0.9123	pathogenic	-1.565	Destabilizing	1.0	D	0.829	deleterious	N	0.486572977	None	None	N
K/V	0.8947	likely_pathogenic	0.8724	pathogenic	-0.377	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
K/W	0.9743	likely_pathogenic	0.9673	pathogenic	-0.671	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/Y	0.9247	likely_pathogenic	0.9135	pathogenic	-0.309	Destabilizing	1.0	D	0.893	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.