TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28334	85225;85226;85227	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
N2AB	26693	80302;80303;80304	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
N2A	25766	77521;77522;77523	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
N2B	19269	58030;58031;58032	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
Novex-1	19394	58405;58406;58407	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
Novex-2	19461	58606;58607;58608	chr2:178561132;178561131;178561130	chr2:179425859;179425858;179425857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-94
• Domain position: 83
• Structural Position: 115
• Q(SASA): 0.7214
• 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
D/N	None	None	0.684	N	0.35	0.244	0.28722502521	gnomAD-4.0.0	6.84207E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15934E-05	0
D/Y	None	None	0.979	N	0.553	0.481	0.44153150616	gnomAD-4.0.0	6.84207E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99447E-07	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
D/A	0.2091	likely_benign	0.1863	benign	-0.116	Destabilizing	0.309	N	0.489	neutral	N	0.430318313	None	None	I
D/C	0.6335	likely_pathogenic	0.6295	pathogenic	0.242	Stabilizing	0.996	D	0.536	neutral	None	None	None	None	I
D/E	0.1989	likely_benign	0.1909	benign	-0.218	Destabilizing	0.012	N	0.194	neutral	N	0.401035556	None	None	I
D/F	0.6595	likely_pathogenic	0.6517	pathogenic	-0.302	Destabilizing	0.984	D	0.552	neutral	None	None	None	None	I
D/G	0.0977	likely_benign	0.0988	benign	-0.263	Destabilizing	0.001	N	0.267	neutral	N	0.200906637	None	None	I
D/H	0.3874	ambiguous	0.3605	ambiguous	-0.089	Destabilizing	0.979	D	0.553	neutral	N	0.468452626	None	None	I
D/I	0.5938	likely_pathogenic	0.5686	pathogenic	0.205	Stabilizing	0.984	D	0.551	neutral	None	None	None	None	I
D/K	0.5038	ambiguous	0.4589	ambiguous	0.47	Stabilizing	0.742	D	0.462	neutral	None	None	None	None	I
D/L	0.4551	ambiguous	0.4317	ambiguous	0.205	Stabilizing	0.854	D	0.577	neutral	None	None	None	None	I
D/M	0.7061	likely_pathogenic	0.6864	pathogenic	0.346	Stabilizing	0.996	D	0.531	neutral	None	None	None	None	I
D/N	0.1034	likely_benign	0.1041	benign	0.358	Stabilizing	0.684	D	0.35	neutral	N	0.419794675	None	None	I
D/P	0.899	likely_pathogenic	0.8574	pathogenic	0.119	Stabilizing	0.947	D	0.543	neutral	None	None	None	None	I
D/Q	0.4289	ambiguous	0.3841	ambiguous	0.347	Stabilizing	0.742	D	0.385	neutral	None	None	None	None	I
D/R	0.5146	ambiguous	0.4633	ambiguous	0.548	Stabilizing	0.91	D	0.57	neutral	None	None	None	None	I
D/S	0.1461	likely_benign	0.1389	benign	0.236	Stabilizing	0.543	D	0.357	neutral	None	None	None	None	I
D/T	0.3841	ambiguous	0.3547	ambiguous	0.342	Stabilizing	0.854	D	0.511	neutral	None	None	None	None	I
D/V	0.381	ambiguous	0.3534	ambiguous	0.119	Stabilizing	0.815	D	0.577	neutral	N	0.467759193	None	None	I
D/W	0.9175	likely_pathogenic	0.9154	pathogenic	-0.263	Destabilizing	0.996	D	0.547	neutral	None	None	None	None	I
D/Y	0.2955	likely_benign	0.2892	benign	-0.081	Destabilizing	0.979	D	0.553	neutral	N	0.44925079	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.