TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7956	24091;24092;24093	chr2:178719626;178719625;178719624	chr2:179584353;179584352;179584351
N2AB	7639	23140;23141;23142	chr2:178719626;178719625;178719624	chr2:179584353;179584352;179584351
N2A	6712	20359;20360;20361	chr2:178719626;178719625;178719624	chr2:179584353;179584352;179584351
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-64
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.5475
• 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/I	rs1405929725	None	0.642	N	0.549	0.28	0.561599553422	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/I	rs1405929725	None	0.642	N	0.549	0.28	0.561599553422	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47024E-05	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	0.2292	likely_benign	0.2257	benign	-0.475	Destabilizing	0.176	N	0.257	neutral	None	None	None	None	N
K/C	0.6635	likely_pathogenic	0.6798	pathogenic	-0.276	Destabilizing	0.995	D	0.435	neutral	None	None	None	None	N
K/D	0.476	ambiguous	0.4725	ambiguous	-0.124	Destabilizing	0.329	N	0.401	neutral	None	None	None	None	N
K/E	0.1065	likely_benign	0.1076	benign	-0.035	Destabilizing	0.01	N	0.158	neutral	N	0.422291554	None	None	N
K/F	0.7753	likely_pathogenic	0.7976	pathogenic	-0.209	Destabilizing	0.981	D	0.469	neutral	None	None	None	None	N
K/G	0.3084	likely_benign	0.3247	benign	-0.83	Destabilizing	0.329	N	0.345	neutral	None	None	None	None	N
K/H	0.3403	ambiguous	0.3396	benign	-1.279	Destabilizing	0.944	D	0.495	neutral	None	None	None	None	N
K/I	0.3543	ambiguous	0.3676	ambiguous	0.438	Stabilizing	0.642	D	0.549	neutral	N	0.485652386	None	None	N
K/L	0.3781	ambiguous	0.3962	ambiguous	0.438	Stabilizing	0.495	N	0.377	neutral	None	None	None	None	N
K/M	0.198	likely_benign	0.2036	benign	0.408	Stabilizing	0.981	D	0.497	neutral	None	None	None	None	N
K/N	0.3428	ambiguous	0.3441	ambiguous	-0.245	Destabilizing	0.425	N	0.387	neutral	N	0.477590263	None	None	N
K/P	0.7987	likely_pathogenic	0.8149	pathogenic	0.164	Stabilizing	0.828	D	0.481	neutral	None	None	None	None	N
K/Q	0.1151	likely_benign	0.1129	benign	-0.336	Destabilizing	0.065	N	0.188	neutral	N	0.448691508	None	None	N
K/R	0.0781	likely_benign	0.0771	benign	-0.606	Destabilizing	0.002	N	0.127	neutral	N	0.472837805	None	None	N
K/S	0.2584	likely_benign	0.255	benign	-0.841	Destabilizing	0.013	N	0.139	neutral	None	None	None	None	N
K/T	0.1196	likely_benign	0.1177	benign	-0.554	Destabilizing	0.01	N	0.196	neutral	N	0.409999834	None	None	N
K/V	0.3135	likely_benign	0.3187	benign	0.164	Stabilizing	0.704	D	0.465	neutral	None	None	None	None	N
K/W	0.7952	likely_pathogenic	0.8059	pathogenic	-0.112	Destabilizing	0.995	D	0.453	neutral	None	None	None	None	N
K/Y	0.6156	likely_pathogenic	0.6327	pathogenic	0.164	Stabilizing	0.981	D	0.511	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.