TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9735	29428;29429;29430	chr2:178706671;178706670;178706669	chr2:179571398;179571397;179571396
N2AB	9418	28477;28478;28479	chr2:178706671;178706670;178706669	chr2:179571398;179571397;179571396
N2A	8491	25696;25697;25698	chr2:178706671;178706670;178706669	chr2:179571398;179571397;179571396
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-83
• Domain position: 38
• Structural Position: 52
• Q(SASA): 0.3767
• 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	rs760884958	0.25	1.0	None	0.702	0.165	0.128392430309	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
K/N	rs760884958	0.25	1.0	None	0.702	0.165	0.128392430309	gnomAD-4.0.0	6.84189E-07	None	None	None	None	N	None	0	2.23614E-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
K/A	0.9597	likely_pathogenic	0.931	pathogenic	-0.177	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
K/C	0.992	likely_pathogenic	0.9863	pathogenic	-0.701	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.9771	likely_pathogenic	0.9625	pathogenic	-0.374	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/E	0.935	likely_pathogenic	0.8666	pathogenic	-0.373	Destabilizing	0.999	D	0.57	neutral	None	None	None	None	N
K/F	0.9938	likely_pathogenic	0.9862	pathogenic	-0.573	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/G	0.9591	likely_pathogenic	0.9316	pathogenic	-0.285	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/H	0.9238	likely_pathogenic	0.8645	pathogenic	-0.339	Destabilizing	1.0	D	0.664	neutral	None	None	None	None	N
K/I	0.9538	likely_pathogenic	0.914	pathogenic	0.032	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/L	0.9419	likely_pathogenic	0.8983	pathogenic	0.032	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/M	0.926	likely_pathogenic	0.862	pathogenic	-0.424	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
K/N	0.9507	likely_pathogenic	0.9176	pathogenic	-0.268	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
K/P	0.9396	likely_pathogenic	0.906	pathogenic	-0.017	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
K/Q	0.8427	likely_pathogenic	0.7197	pathogenic	-0.34	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
K/R	0.2379	likely_benign	0.1907	benign	-0.189	Destabilizing	0.999	D	0.529	neutral	None	None	None	None	N
K/S	0.9628	likely_pathogenic	0.9331	pathogenic	-0.583	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
K/T	0.9101	likely_pathogenic	0.8521	pathogenic	-0.467	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/V	0.9525	likely_pathogenic	0.9158	pathogenic	-0.017	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
K/W	0.991	likely_pathogenic	0.9793	pathogenic	-0.706	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/Y	0.9768	likely_pathogenic	0.9569	pathogenic	-0.364	Destabilizing	1.0	D	0.679	prob.neutral	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.