TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28433	85522;85523;85524	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
N2AB	26792	80599;80600;80601	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
N2A	25865	77818;77819;77820	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
N2B	19368	58327;58328;58329	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
Novex-1	19493	58702;58703;58704	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
Novex-2	19560	58903;58904;58905	chr2:178560835;178560834;178560833	chr2:179425562;179425561;179425560
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-143
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.5995
• Predicted PPI site: I

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	rs1444500550	0.261	0.081	N	0.306	0.146	0.183819452728	gnomAD-2.1.1	1.21E-05	None	None	None	None	I	None	0	0	None	0	1.68105E-04	None	0	None	0	0	0
K/N	rs1444500550	0.261	0.081	N	0.306	0.146	0.183819452728	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs1444500550	0.261	0.081	N	0.306	0.146	0.183819452728	gnomAD-4.0.0	3.1832E-06	None	None	None	None	I	None	0	0	None	0	5.55988E-05	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	0.4464	ambiguous	0.4454	ambiguous	-0.239	Destabilizing	0.025	N	0.338	neutral	None	None	None	None	I
K/C	0.619	likely_pathogenic	0.6016	pathogenic	-0.313	Destabilizing	0.958	D	0.413	neutral	None	None	None	None	I
K/D	0.7148	likely_pathogenic	0.7067	pathogenic	0.083	Stabilizing	0.104	N	0.377	neutral	None	None	None	None	I
K/E	0.1934	likely_benign	0.2013	benign	0.101	Stabilizing	0.019	N	0.227	neutral	N	0.487055109	None	None	I
K/F	0.8456	likely_pathogenic	0.8366	pathogenic	-0.448	Destabilizing	0.667	D	0.443	neutral	None	None	None	None	I
K/G	0.5741	likely_pathogenic	0.5507	ambiguous	-0.477	Destabilizing	0.055	N	0.445	neutral	None	None	None	None	I
K/H	0.2531	likely_benign	0.2475	benign	-0.925	Destabilizing	None	N	0.197	neutral	None	None	None	None	I
K/I	0.476	ambiguous	0.4813	ambiguous	0.317	Stabilizing	0.667	D	0.467	neutral	None	None	None	None	I
K/L	0.474	ambiguous	0.4678	ambiguous	0.317	Stabilizing	0.104	N	0.414	neutral	None	None	None	None	I
K/M	0.2783	likely_benign	0.279	benign	0.366	Stabilizing	0.602	D	0.408	neutral	D	0.536523924	None	None	I
K/N	0.481	ambiguous	0.4706	ambiguous	0.103	Stabilizing	0.081	N	0.306	neutral	N	0.485847822	None	None	I
K/P	0.9699	likely_pathogenic	0.9623	pathogenic	0.161	Stabilizing	0.364	N	0.472	neutral	None	None	None	None	I
K/Q	0.097	likely_benign	0.0972	benign	-0.158	Destabilizing	None	N	0.134	neutral	N	0.463660961	None	None	I
K/R	0.0787	likely_benign	0.0795	benign	-0.143	Destabilizing	None	N	0.139	neutral	N	0.504507506	None	None	I
K/S	0.3958	ambiguous	0.3967	ambiguous	-0.511	Destabilizing	0.002	N	0.155	neutral	None	None	None	None	I
K/T	0.15	likely_benign	0.1598	benign	-0.33	Destabilizing	0.042	N	0.373	neutral	N	0.477760835	None	None	I
K/V	0.4097	ambiguous	0.4185	ambiguous	0.161	Stabilizing	0.22	N	0.457	neutral	None	None	None	None	I
K/W	0.7625	likely_pathogenic	0.7509	pathogenic	-0.355	Destabilizing	0.958	D	0.425	neutral	None	None	None	None	I
K/Y	0.6809	likely_pathogenic	0.6675	pathogenic	0.006	Stabilizing	0.22	N	0.463	neutral	None	None	None	None	I

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.