TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15879	47860;47861;47862	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
N2AB	14238	42937;42938;42939	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
N2A	13311	40156;40157;40158	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
N2B	6814	20665;20666;20667	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
Novex-1	6939	21040;21041;21042	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
Novex-2	7006	21241;21242;21243	chr2:178617450;178617449;178617448	chr2:179482177;179482176;179482175
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: Fn3-3
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3157
• 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/Q	rs2057553844	None	0.065	N	0.307	0.047	0.154104182512	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/Q	rs2057553844	None	0.065	N	0.307	0.047	0.154104182512	gnomAD-4.0.0	6.58345E-06	None	None	None	None	I	None	2.41488E-05	0	None	0	0	None	0	0	0	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	0.1374	likely_benign	0.1562	benign	-0.95	Destabilizing	0.002	N	0.263	neutral	None	None	None	None	I
K/C	0.3881	ambiguous	0.4131	ambiguous	-0.99	Destabilizing	0.245	N	0.537	neutral	None	None	None	None	I
K/D	0.3617	ambiguous	0.4346	ambiguous	-0.798	Destabilizing	0.018	N	0.361	neutral	None	None	None	None	I
K/E	0.1275	likely_benign	0.1515	benign	-0.585	Destabilizing	0.006	N	0.269	neutral	N	0.464221274	None	None	I
K/F	0.3873	ambiguous	0.4985	ambiguous	-0.322	Destabilizing	0.085	N	0.549	neutral	None	None	None	None	I
K/G	0.2667	likely_benign	0.3224	benign	-1.409	Destabilizing	0.004	N	0.372	neutral	None	None	None	None	I
K/H	0.168	likely_benign	0.1948	benign	-1.664	Destabilizing	0.497	N	0.465	neutral	None	None	None	None	I
K/I	0.1217	likely_benign	0.1556	benign	0.301	Stabilizing	None	N	0.432	neutral	N	0.481625202	None	None	I
K/L	0.145	likely_benign	0.1928	benign	0.301	Stabilizing	0.002	N	0.385	neutral	None	None	None	None	I
K/M	0.0879	likely_benign	0.1024	benign	0.079	Stabilizing	0.245	N	0.52	neutral	None	None	None	None	I
K/N	0.1655	likely_benign	0.2188	benign	-1.131	Destabilizing	0.014	N	0.266	neutral	N	0.479222097	None	None	I
K/P	0.8706	likely_pathogenic	0.9128	pathogenic	-0.088	Destabilizing	0.037	N	0.369	neutral	None	None	None	None	I
K/Q	0.087	likely_benign	0.0978	benign	-0.979	Destabilizing	0.065	N	0.307	neutral	N	0.463362112	None	None	I
K/R	0.0813	likely_benign	0.0885	benign	-0.922	Destabilizing	0.014	N	0.339	neutral	N	0.468452861	None	None	I
K/S	0.1364	likely_benign	0.1618	benign	-1.757	Destabilizing	None	N	0.1	neutral	None	None	None	None	I
K/T	0.0492	likely_benign	0.0546	benign	-1.3	Destabilizing	None	N	0.204	neutral	N	0.370868746	None	None	I
K/V	0.1399	likely_benign	0.1694	benign	-0.088	Destabilizing	0.002	N	0.386	neutral	None	None	None	None	I
K/W	0.5329	ambiguous	0.6129	pathogenic	-0.277	Destabilizing	0.788	D	0.553	neutral	None	None	None	None	I
K/Y	0.3333	likely_benign	0.4059	ambiguous	0.044	Stabilizing	0.085	N	0.585	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.