TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24189	72790;72791;72792	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
N2AB	22548	67867;67868;67869	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
N2A	21621	65086;65087;65088	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
N2B	15124	45595;45596;45597	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
Novex-1	15249	45970;45971;45972	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
Novex-2	15316	46171;46172;46173	chr2:178573567;178573566;178573565	chr2:179438294;179438293;179438292
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: Fn3-63
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.7816
• 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/R	None	None	0.977	N	0.651	0.282	0.457922657367	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.228	likely_benign	0.2516	benign	-0.04	Destabilizing	0.983	D	0.599	neutral	None	None	None	None	N
K/C	0.5661	likely_pathogenic	0.6205	pathogenic	-0.125	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/D	0.5212	ambiguous	0.5634	ambiguous	0.114	Stabilizing	0.966	D	0.653	neutral	None	None	None	None	N
K/E	0.1409	likely_benign	0.1421	benign	0.116	Stabilizing	0.117	N	0.276	neutral	N	0.404193291	None	None	N
K/F	0.7375	likely_pathogenic	0.7695	pathogenic	-0.278	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/G	0.4053	ambiguous	0.421	ambiguous	-0.246	Destabilizing	0.995	D	0.641	neutral	None	None	None	None	N
K/H	0.2546	likely_benign	0.2835	benign	-0.616	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
K/I	0.3366	likely_benign	0.3679	ambiguous	0.424	Stabilizing	0.997	D	0.738	prob.delet.	D	0.523983409	None	None	N
K/L	0.3167	likely_benign	0.3444	ambiguous	0.424	Stabilizing	0.995	D	0.651	neutral	None	None	None	None	N
K/M	0.2181	likely_benign	0.2374	benign	0.375	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
K/N	0.3901	ambiguous	0.4285	ambiguous	0.304	Stabilizing	0.993	D	0.725	prob.delet.	N	0.498143602	None	None	N
K/P	0.3049	likely_benign	0.3382	benign	0.298	Stabilizing	0.998	D	0.673	neutral	None	None	None	None	N
K/Q	0.1031	likely_benign	0.1078	benign	0.074	Stabilizing	0.987	D	0.718	prob.delet.	N	0.452083238	None	None	N
K/R	0.081	likely_benign	0.0809	benign	0.006	Stabilizing	0.977	D	0.651	neutral	N	0.494815295	None	None	N
K/S	0.3331	likely_benign	0.3656	ambiguous	-0.23	Destabilizing	0.983	D	0.65	neutral	None	None	None	None	N
K/T	0.1571	likely_benign	0.183	benign	-0.077	Destabilizing	0.993	D	0.671	neutral	N	0.514766493	None	None	N
K/V	0.2875	likely_benign	0.3109	benign	0.298	Stabilizing	0.998	D	0.694	prob.neutral	None	None	None	None	N
K/W	0.7214	likely_pathogenic	0.7464	pathogenic	-0.251	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/Y	0.5939	likely_pathogenic	0.6369	pathogenic	0.11	Stabilizing	0.999	D	0.695	prob.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.