TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33392	100399;100400;100401	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
N2AB	31751	95476;95477;95478	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
N2A	30824	92695;92696;92697	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
N2B	24327	73204;73205;73206	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
Novex-1	24452	73579;73580;73581	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
Novex-2	24519	73780;73781;73782	chr2:178536573;178536572;178536571	chr2:179401300;179401299;179401298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-131
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.7485
• 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/R	rs1363009157	0.29	0.012	N	0.296	0.136	0.17948927462	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
K/R	rs1363009157	0.29	0.012	N	0.296	0.136	0.17948927462	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1363009157	0.29	0.012	N	0.296	0.136	0.17948927462	gnomAD-4.0.0	6.56927E-06	None	None	None	None	I	None	2.4115E-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	0.5227	ambiguous	0.4947	ambiguous	-0.155	Destabilizing	0.717	D	0.56	neutral	None	None	None	None	I
K/C	0.834	likely_pathogenic	0.7725	pathogenic	-0.247	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	I
K/D	0.8471	likely_pathogenic	0.8436	pathogenic	0.196	Stabilizing	0.947	D	0.551	neutral	None	None	None	None	I
K/E	0.3864	ambiguous	0.3693	ambiguous	0.191	Stabilizing	0.657	D	0.535	neutral	N	0.464220242	None	None	I
K/F	0.8636	likely_pathogenic	0.8502	pathogenic	-0.464	Destabilizing	0.998	D	0.809	deleterious	None	None	None	None	I
K/G	0.754	likely_pathogenic	0.7215	pathogenic	-0.34	Destabilizing	0.835	D	0.519	neutral	None	None	None	None	I
K/H	0.5637	ambiguous	0.5205	ambiguous	-0.706	Destabilizing	0.993	D	0.603	neutral	None	None	None	None	I
K/I	0.3326	likely_benign	0.3304	benign	0.249	Stabilizing	0.973	D	0.843	deleterious	None	None	None	None	I
K/L	0.4524	ambiguous	0.423	ambiguous	0.249	Stabilizing	0.835	D	0.519	neutral	None	None	None	None	I
K/M	0.2855	likely_benign	0.2813	benign	0.276	Stabilizing	0.99	D	0.595	neutral	N	0.482770634	None	None	I
K/N	0.5906	likely_pathogenic	0.5864	pathogenic	0.279	Stabilizing	0.931	D	0.617	neutral	N	0.471667819	None	None	I
K/P	0.6289	likely_pathogenic	0.6004	pathogenic	0.142	Stabilizing	0.973	D	0.668	prob.neutral	None	None	None	None	I
K/Q	0.2368	likely_benign	0.2103	benign	0.012	Stabilizing	0.106	N	0.261	neutral	N	0.519612165	None	None	I
K/R	0.1202	likely_benign	0.1049	benign	0.035	Stabilizing	0.012	N	0.296	neutral	N	0.470876856	None	None	I
K/S	0.6609	likely_pathogenic	0.6513	pathogenic	-0.309	Destabilizing	0.717	D	0.633	neutral	None	None	None	None	I
K/T	0.294	likely_benign	0.2965	benign	-0.167	Destabilizing	0.931	D	0.549	neutral	N	0.469626062	None	None	I
K/V	0.3722	ambiguous	0.3616	ambiguous	0.142	Stabilizing	0.947	D	0.695	prob.delet.	None	None	None	None	I
K/W	0.9321	likely_pathogenic	0.9133	pathogenic	-0.403	Destabilizing	0.998	D	0.881	deleterious	None	None	None	None	I
K/Y	0.7729	likely_pathogenic	0.7539	pathogenic	-0.038	Destabilizing	0.973	D	0.849	deleterious	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.