TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4903	14932;14933;14934	chr2:178735739;178735738;178735737	chr2:179600466;179600465;179600464
N2AB	4586	13981;13982;13983	chr2:178735739;178735738;178735737	chr2:179600466;179600465;179600464
N2A	3659	11200;11201;11202	chr2:178735739;178735738;178735737	chr2:179600466;179600465;179600464
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: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-32
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.4265
• 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	rs1060500444	None	0.028	N	0.12	0.118	0.124217242631	gnomAD-4.0.0	1.59139E-06	None	None	None	None	N	None	0	2.28666E-05	None	0	0	None	0	0	0	0	0
K/R	None	None	0.912	N	0.259	0.116	0.241664281697	gnomAD-4.0.0	6.84229E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-07	0	0
K/T	None	None	0.064	N	0.219	0.156	0.166414681773	gnomAD-4.0.0	6.84229E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99454E-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	0.4553	ambiguous	0.5558	ambiguous	-0.182	Destabilizing	0.083	N	0.171	neutral	None	None	None	None	N
K/C	0.7431	likely_pathogenic	0.8095	pathogenic	-0.303	Destabilizing	0.998	D	0.371	neutral	None	None	None	None	N
K/D	0.5584	ambiguous	0.6722	pathogenic	0.138	Stabilizing	0.021	N	0.181	neutral	None	None	None	None	N
K/E	0.1475	likely_benign	0.1919	benign	0.176	Stabilizing	0.514	D	0.279	neutral	N	0.373590786	None	None	N
K/F	0.8577	likely_pathogenic	0.9082	pathogenic	-0.168	Destabilizing	0.993	D	0.394	neutral	None	None	None	None	N
K/G	0.398	ambiguous	0.4979	ambiguous	-0.454	Destabilizing	0.737	D	0.333	neutral	None	None	None	None	N
K/H	0.3381	likely_benign	0.4011	ambiguous	-0.758	Destabilizing	0.98	D	0.329	neutral	None	None	None	None	N
K/I	0.5999	likely_pathogenic	0.6921	pathogenic	0.473	Stabilizing	0.96	D	0.427	neutral	None	None	None	None	N
K/L	0.4998	ambiguous	0.5972	pathogenic	0.473	Stabilizing	0.872	D	0.37	neutral	None	None	None	None	N
K/M	0.3299	likely_benign	0.4098	ambiguous	0.324	Stabilizing	0.991	D	0.328	neutral	N	0.42731809	None	None	N
K/N	0.4319	ambiguous	0.5327	ambiguous	0.037	Stabilizing	0.028	N	0.12	neutral	N	0.390472157	None	None	N
K/P	0.8997	likely_pathogenic	0.9365	pathogenic	0.285	Stabilizing	0.932	D	0.384	neutral	None	None	None	None	N
K/Q	0.1077	likely_benign	0.1311	benign	-0.142	Destabilizing	0.912	D	0.321	neutral	N	0.394513697	None	None	N
K/R	0.0819	likely_benign	0.0887	benign	-0.226	Destabilizing	0.912	D	0.259	neutral	N	0.420461489	None	None	N
K/S	0.4181	ambiguous	0.5225	ambiguous	-0.562	Destabilizing	0.584	D	0.3	neutral	None	None	None	None	N
K/T	0.2422	likely_benign	0.3151	benign	-0.352	Destabilizing	0.064	N	0.219	neutral	N	0.398812978	None	None	N
K/V	0.4981	ambiguous	0.5879	pathogenic	0.285	Stabilizing	0.872	D	0.375	neutral	None	None	None	None	N
K/W	0.7812	likely_pathogenic	0.8463	pathogenic	-0.084	Destabilizing	0.998	D	0.459	neutral	None	None	None	None	N
K/Y	0.6822	likely_pathogenic	0.7581	pathogenic	0.232	Stabilizing	0.993	D	0.365	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.