TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4705	14338;14339;14340	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
N2AB	4388	13387;13388;13389	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
N2A	3461	10606;10607;10608	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
N2B	4342	13249;13250;13251	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
Novex-1	4467	13624;13625;13626	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
Novex-2	4534	13825;13826;13827	chr2:178738340;178738339;178738338	chr2:179603067;179603066;179603065
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-30
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6224
• 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/Q	None	None	0.062	N	0.372	0.178	0.239305524855	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3137	likely_benign	0.3949	ambiguous	-0.164	Destabilizing	0.067	N	0.376	neutral	None	None	None	None	N
K/C	0.4943	ambiguous	0.6064	pathogenic	-0.228	Destabilizing	0.935	D	0.405	neutral	None	None	None	None	N
K/D	0.5531	ambiguous	0.6303	pathogenic	0.092	Stabilizing	0.149	N	0.409	neutral	None	None	None	None	N
K/E	0.1872	likely_benign	0.2301	benign	0.157	Stabilizing	0.027	N	0.38	neutral	N	0.492706242	None	None	N
K/F	0.6697	likely_pathogenic	0.7886	pathogenic	-0.009	Destabilizing	0.555	D	0.411	neutral	None	None	None	None	N
K/G	0.231	likely_benign	0.2933	benign	-0.464	Destabilizing	0.149	N	0.435	neutral	None	None	None	None	N
K/H	0.2223	likely_benign	0.2783	benign	-0.761	Destabilizing	0.555	D	0.389	neutral	None	None	None	None	N
K/I	0.3461	ambiguous	0.4467	ambiguous	0.579	Stabilizing	0.484	N	0.423	neutral	N	0.502632639	None	None	N
K/L	0.3033	likely_benign	0.4068	ambiguous	0.579	Stabilizing	0.149	N	0.435	neutral	None	None	None	None	N
K/M	0.2232	likely_benign	0.282	benign	0.28	Stabilizing	0.791	D	0.387	neutral	None	None	None	None	N
K/N	0.3796	ambiguous	0.4694	ambiguous	0.006	Stabilizing	0.117	N	0.341	neutral	N	0.514285293	None	None	N
K/P	0.3807	ambiguous	0.4413	ambiguous	0.362	Stabilizing	0.555	D	0.386	neutral	None	None	None	None	N
K/Q	0.1031	likely_benign	0.1282	benign	-0.078	Destabilizing	0.062	N	0.372	neutral	N	0.51303778	None	None	N
K/R	0.0496	likely_benign	0.0505	benign	-0.319	Destabilizing	None	N	0.109	neutral	N	0.486667993	None	None	N
K/S	0.3916	ambiguous	0.4973	ambiguous	-0.526	Destabilizing	0.149	N	0.335	neutral	None	None	None	None	N
K/T	0.2108	likely_benign	0.268	benign	-0.281	Destabilizing	0.117	N	0.395	neutral	N	0.510022535	None	None	N
K/V	0.3432	ambiguous	0.4279	ambiguous	0.362	Stabilizing	0.149	N	0.409	neutral	None	None	None	None	N
K/W	0.4462	ambiguous	0.5897	pathogenic	0.031	Stabilizing	0.935	D	0.453	neutral	None	None	None	None	N
K/Y	0.5004	ambiguous	0.608	pathogenic	0.328	Stabilizing	0.555	D	0.417	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.