TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9362	28309;28310;28311	chr2:178711152;178711151;178711150	chr2:179575879;179575878;179575877
N2AB	9045	27358;27359;27360	chr2:178711152;178711151;178711150	chr2:179575879;179575878;179575877
N2A	8118	24577;24578;24579	chr2:178711152;178711151;178711150	chr2:179575879;179575878;179575877
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-79
• Domain position: 62
• Structural Position: 143
• Q(SASA): 0.6297
• 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/E	rs774589686	0.461	0.027	None	0.38	0.053	0.12205267543	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/E	rs774589686	0.461	0.027	None	0.38	0.053	0.12205267543	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/E	rs774589686	0.461	0.027	None	0.38	0.053	0.12205267543	gnomAD-4.0.0	8.11935E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.63927E-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	0.3041	likely_benign	0.256	benign	-0.15	Destabilizing	0.035	N	0.393	neutral	None	None	None	None	N
K/C	0.7173	likely_pathogenic	0.615	pathogenic	-0.11	Destabilizing	0.935	D	0.335	neutral	None	None	None	None	N
K/D	0.465	ambiguous	0.4383	ambiguous	0.089	Stabilizing	0.081	N	0.381	neutral	None	None	None	None	N
K/E	0.1425	likely_benign	0.1125	benign	0.127	Stabilizing	0.027	N	0.38	neutral	None	None	None	None	N
K/F	0.7013	likely_pathogenic	0.6478	pathogenic	-0.156	Destabilizing	0.791	D	0.339	neutral	None	None	None	None	N
K/G	0.4244	ambiguous	0.3593	ambiguous	-0.433	Destabilizing	0.001	N	0.194	neutral	None	None	None	None	N
K/H	0.238	likely_benign	0.1938	benign	-0.825	Destabilizing	0.38	N	0.329	neutral	None	None	None	None	N
K/I	0.3935	ambiguous	0.3229	benign	0.539	Stabilizing	0.484	N	0.356	neutral	None	None	None	None	N
K/L	0.3224	likely_benign	0.2663	benign	0.539	Stabilizing	0.149	N	0.382	neutral	None	None	None	None	N
K/M	0.2492	likely_benign	0.1885	benign	0.507	Stabilizing	0.555	D	0.333	neutral	None	None	None	None	N
K/N	0.3164	likely_benign	0.2961	benign	0.142	Stabilizing	None	N	0.276	neutral	None	None	None	None	N
K/P	0.7773	likely_pathogenic	0.7913	pathogenic	0.34	Stabilizing	0.555	D	0.355	neutral	None	None	None	None	N
K/Q	0.1003	likely_benign	0.0764	benign	-0.049	Destabilizing	None	N	0.151	neutral	None	None	None	None	N
K/R	0.0921	likely_benign	0.0739	benign	-0.178	Destabilizing	None	N	0.157	neutral	None	None	None	None	N
K/S	0.2862	likely_benign	0.2536	benign	-0.443	Destabilizing	0.035	N	0.321	neutral	None	None	None	None	N
K/T	0.1753	likely_benign	0.1363	benign	-0.231	Destabilizing	0.117	N	0.369	neutral	None	None	None	None	N
K/V	0.3609	ambiguous	0.2867	benign	0.34	Stabilizing	0.149	N	0.355	neutral	None	None	None	None	N
K/W	0.7108	likely_pathogenic	0.6603	pathogenic	-0.086	Destabilizing	0.935	D	0.396	neutral	None	None	None	None	N
K/Y	0.5251	ambiguous	0.4768	ambiguous	0.241	Stabilizing	0.555	D	0.339	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.