TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27209	81850;81851;81852	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
N2AB	25568	76927;76928;76929	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
N2A	24641	74146;74147;74148	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
N2B	18144	54655;54656;54657	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
Novex-1	18269	55030;55031;55032	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
Novex-2	18336	55231;55232;55233	chr2:178564507;178564506;178564505	chr2:179429234;179429233;179429232
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: Fn3-86
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1656
• 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	0.549	N	0.603	0.374	0.249502417897	gnomAD-4.0.0	6.84885E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00001E-07	0	0
K/R	None	None	0.002	N	0.269	0.092	0.215109475489	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-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	0.9602	likely_pathogenic	0.9295	pathogenic	-1.459	Destabilizing	0.25	N	0.559	neutral	None	None	None	None	N
K/C	0.8934	likely_pathogenic	0.8294	pathogenic	-1.51	Destabilizing	0.992	D	0.731	prob.delet.	None	None	None	None	N
K/D	0.9961	likely_pathogenic	0.9937	pathogenic	-2.247	Highly Destabilizing	0.92	D	0.625	neutral	None	None	None	None	N
K/E	0.9077	likely_pathogenic	0.8413	pathogenic	-1.918	Destabilizing	0.549	D	0.621	neutral	N	0.506109264	None	None	N
K/F	0.9783	likely_pathogenic	0.9502	pathogenic	-0.662	Destabilizing	0.85	D	0.722	prob.delet.	None	None	None	None	N
K/G	0.9694	likely_pathogenic	0.9484	pathogenic	-1.963	Destabilizing	0.617	D	0.631	neutral	None	None	None	None	N
K/H	0.8093	likely_pathogenic	0.7194	pathogenic	-1.776	Destabilizing	0.92	D	0.649	neutral	None	None	None	None	N
K/I	0.9127	likely_pathogenic	0.8455	pathogenic	-0.011	Destabilizing	0.739	D	0.71	prob.delet.	None	None	None	None	N
K/L	0.8695	likely_pathogenic	0.7833	pathogenic	-0.011	Destabilizing	0.103	N	0.619	neutral	None	None	None	None	N
K/M	0.6683	likely_pathogenic	0.5047	ambiguous	-0.382	Destabilizing	0.036	N	0.492	neutral	N	0.517249438	None	None	N
K/N	0.9789	likely_pathogenic	0.961	pathogenic	-2.061	Highly Destabilizing	0.549	D	0.603	neutral	N	0.501336324	None	None	N
K/P	0.9991	likely_pathogenic	0.9989	pathogenic	-0.476	Destabilizing	0.972	D	0.642	neutral	None	None	None	None	N
K/Q	0.5225	ambiguous	0.3944	ambiguous	-1.621	Destabilizing	0.549	D	0.632	neutral	N	0.484713326	None	None	N
K/R	0.1102	likely_benign	0.0999	benign	-1.044	Destabilizing	0.002	N	0.269	neutral	N	0.432420042	None	None	N
K/S	0.9707	likely_pathogenic	0.9441	pathogenic	-2.532	Highly Destabilizing	0.617	D	0.613	neutral	None	None	None	None	N
K/T	0.8983	likely_pathogenic	0.8242	pathogenic	-1.936	Destabilizing	0.549	D	0.579	neutral	N	0.477356266	None	None	N
K/V	0.8717	likely_pathogenic	0.7904	pathogenic	-0.476	Destabilizing	0.447	N	0.627	neutral	None	None	None	None	N
K/W	0.9601	likely_pathogenic	0.92	pathogenic	-0.78	Destabilizing	0.992	D	0.746	deleterious	None	None	None	None	N
K/Y	0.9039	likely_pathogenic	0.8211	pathogenic	-0.423	Destabilizing	0.92	D	0.694	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.