TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22473	67642;67643;67644	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
N2AB	20832	62719;62720;62721	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
N2A	19905	59938;59939;59940	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
N2B	13408	40447;40448;40449	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
Novex-1	13533	40822;40823;40824	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
Novex-2	13600	41023;41024;41025	chr2:178579780;178579779;178579778	chr2:179444507;179444506;179444505
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: Fn3-51
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.7238
• 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/E	rs1164219894	0.178	0.996	N	0.575	0.371	0.272639205421	gnomAD-4.0.0	2.05323E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.69903E-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	0.5532	ambiguous	0.5003	ambiguous	-0.418	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	I
K/C	0.8208	likely_pathogenic	0.7815	pathogenic	-0.51	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	I
K/D	0.7169	likely_pathogenic	0.6858	pathogenic	-0.09	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	I
K/E	0.2567	likely_benign	0.2375	benign	0.018	Stabilizing	0.996	D	0.575	neutral	N	0.47626682	None	None	I
K/F	0.8989	likely_pathogenic	0.8955	pathogenic	-0.089	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/G	0.5645	likely_pathogenic	0.5042	ambiguous	-0.768	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/H	0.4871	ambiguous	0.4407	ambiguous	-0.992	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
K/I	0.5379	ambiguous	0.5458	ambiguous	0.481	Stabilizing	1.0	D	0.693	prob.neutral	D	0.523927481	None	None	I
K/L	0.5056	ambiguous	0.466	ambiguous	0.481	Stabilizing	1.0	D	0.611	neutral	None	None	None	None	I
K/M	0.3453	ambiguous	0.3306	benign	0.164	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
K/N	0.5028	ambiguous	0.4763	ambiguous	-0.415	Destabilizing	0.999	D	0.688	prob.neutral	N	0.470362355	None	None	I
K/P	0.942	likely_pathogenic	0.9224	pathogenic	0.212	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	I
K/Q	0.1612	likely_benign	0.1429	benign	-0.429	Destabilizing	0.999	D	0.675	neutral	N	0.505032289	None	None	I
K/R	0.096	likely_benign	0.0923	benign	-0.531	Destabilizing	0.64	D	0.319	neutral	N	0.498453033	None	None	I
K/S	0.5627	ambiguous	0.5112	ambiguous	-0.988	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	I
K/T	0.2912	likely_benign	0.2549	benign	-0.679	Destabilizing	0.999	D	0.69	prob.neutral	N	0.471765077	None	None	I
K/V	0.4833	ambiguous	0.463	ambiguous	0.212	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
K/W	0.886	likely_pathogenic	0.8726	pathogenic	-0.024	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
K/Y	0.7991	likely_pathogenic	0.7878	pathogenic	0.252	Stabilizing	1.0	D	0.692	prob.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.