TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6774	20545;20546;20547	chr2:178726002;178726001;178726000	chr2:179590729;179590728;179590727
N2AB	6457	19594;19595;19596	chr2:178726002;178726001;178726000	chr2:179590729;179590728;179590727
N2A	5530	16813;16814;16815	chr2:178726002;178726001;178726000	chr2:179590729;179590728;179590727
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: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-52
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.5107
• 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/R	rs776943120	-0.019	0.001	N	0.235	0.114	0.322230723748	gnomAD-2.1.1	4.21E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.2E-06	0
K/R	rs776943120	-0.019	0.001	N	0.235	0.114	0.322230723748	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
K/R	rs776943120	-0.019	0.001	N	0.235	0.114	0.322230723748	gnomAD-4.0.0	3.13377E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.27495E-06	0	0
K/T	None	None	0.712	N	0.557	0.408	0.513560046879	gnomAD-4.0.0	6.92817E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.07782E-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
K/A	0.4653	ambiguous	0.45	ambiguous	-0.11	Destabilizing	0.757	D	0.546	neutral	None	None	None	None	I
K/C	0.8097	likely_pathogenic	0.7997	pathogenic	-0.244	Destabilizing	0.996	D	0.744	deleterious	None	None	None	None	I
K/D	0.6986	likely_pathogenic	0.676	pathogenic	0.169	Stabilizing	0.957	D	0.583	neutral	None	None	None	None	I
K/E	0.2315	likely_benign	0.2182	benign	0.216	Stabilizing	0.413	N	0.494	neutral	N	0.490578203	None	None	I
K/F	0.8511	likely_pathogenic	0.8402	pathogenic	-0.122	Destabilizing	0.99	D	0.687	prob.neutral	None	None	None	None	I
K/G	0.5435	ambiguous	0.5125	ambiguous	-0.38	Destabilizing	0.916	D	0.529	neutral	None	None	None	None	I
K/H	0.4184	ambiguous	0.3817	ambiguous	-0.694	Destabilizing	0.972	D	0.569	neutral	None	None	None	None	I
K/I	0.4964	ambiguous	0.4933	ambiguous	0.54	Stabilizing	0.329	N	0.7	prob.neutral	N	0.517172946	None	None	I
K/L	0.4756	ambiguous	0.461	ambiguous	0.54	Stabilizing	0.243	N	0.529	neutral	None	None	None	None	I
K/M	0.3974	ambiguous	0.3838	ambiguous	0.302	Stabilizing	0.968	D	0.561	neutral	None	None	None	None	I
K/N	0.5503	ambiguous	0.5185	ambiguous	0.102	Stabilizing	0.892	D	0.583	neutral	N	0.517406113	None	None	I
K/P	0.5044	ambiguous	0.5108	ambiguous	0.353	Stabilizing	0.985	D	0.569	neutral	None	None	None	None	I
K/Q	0.1632	likely_benign	0.14	benign	-0.017	Destabilizing	0.499	N	0.587	neutral	N	0.49566778	None	None	I
K/R	0.0846	likely_benign	0.078	benign	-0.17	Destabilizing	0.001	N	0.235	neutral	N	0.50647595	None	None	I
K/S	0.5568	ambiguous	0.5234	ambiguous	-0.454	Destabilizing	0.757	D	0.543	neutral	None	None	None	None	I
K/T	0.3343	likely_benign	0.3236	benign	-0.229	Destabilizing	0.712	D	0.557	neutral	N	0.49459137	None	None	I
K/V	0.4885	ambiguous	0.4816	ambiguous	0.353	Stabilizing	0.462	N	0.62	neutral	None	None	None	None	I
K/W	0.7973	likely_pathogenic	0.7881	pathogenic	-0.088	Destabilizing	0.997	D	0.752	deleterious	None	None	None	None	I
K/Y	0.7264	likely_pathogenic	0.7066	pathogenic	0.246	Stabilizing	0.759	D	0.648	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.