TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23072	69439;69440;69441	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
N2AB	21431	64516;64517;64518	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
N2A	20504	61735;61736;61737	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
N2B	14007	42244;42245;42246	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
Novex-1	14132	42619;42620;42621	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
Novex-2	14199	42820;42821;42822	chr2:178577121;178577120;178577119	chr2:179441848;179441847;179441846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-55
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.2014
• 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
I/M	rs374117511	-0.843	0.991	D	0.727	0.41	None	gnomAD-2.1.1	5.24E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.15842E-04	0
I/M	rs374117511	-0.843	0.991	D	0.727	0.41	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
I/M	rs374117511	-0.843	0.991	D	0.727	0.41	None	gnomAD-4.0.0	3.46172E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.50711E-05	1.34077E-05	8.53777E-05
I/N	rs1309205725	-1.646	0.997	D	0.819	0.578	0.897848762137	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14837E-04	0	None	0	0	None	0	None	0	0	0
I/N	rs1309205725	-1.646	0.997	D	0.819	0.578	0.897848762137	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	1.47E-05	0	0
I/N	rs1309205725	-1.646	0.997	D	0.819	0.578	0.897848762137	gnomAD-4.0.0	7.43903E-06	None	None	None	None	I	None	1.33608E-05	0	None	0	0	None	0	0	9.32575E-06	0	0
I/V	rs2046609808	None	0.02	N	0.244	0.112	0.433491693731	gnomAD-4.0.0	3.18451E-06	None	None	None	None	I	None	0	2.28676E-05	None	0	0	None	0	0	2.86E-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
I/A	0.9347	likely_pathogenic	0.9481	pathogenic	-2.279	Highly Destabilizing	0.91	D	0.677	prob.neutral	None	None	None	None	I
I/C	0.9507	likely_pathogenic	0.9584	pathogenic	-1.445	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	I
I/D	0.9978	likely_pathogenic	0.9985	pathogenic	-2.051	Highly Destabilizing	0.998	D	0.81	deleterious	None	None	None	None	I
I/E	0.9907	likely_pathogenic	0.9925	pathogenic	-1.95	Destabilizing	0.993	D	0.81	deleterious	None	None	None	None	I
I/F	0.8841	likely_pathogenic	0.9112	pathogenic	-1.512	Destabilizing	0.991	D	0.755	deleterious	D	0.560416164	None	None	I
I/G	0.9893	likely_pathogenic	0.9929	pathogenic	-2.715	Highly Destabilizing	0.993	D	0.8	deleterious	None	None	None	None	I
I/H	0.9938	likely_pathogenic	0.9954	pathogenic	-1.986	Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	I
I/K	0.9851	likely_pathogenic	0.987	pathogenic	-1.654	Destabilizing	0.993	D	0.808	deleterious	None	None	None	None	I
I/L	0.2626	likely_benign	0.2707	benign	-1.085	Destabilizing	0.58	D	0.461	neutral	N	0.485023403	None	None	I
I/M	0.466	ambiguous	0.5173	ambiguous	-0.824	Destabilizing	0.991	D	0.727	prob.delet.	D	0.551594754	None	None	I
I/N	0.969	likely_pathogenic	0.9761	pathogenic	-1.651	Destabilizing	0.997	D	0.819	deleterious	D	0.563965018	None	None	I
I/P	0.9488	likely_pathogenic	0.9499	pathogenic	-1.457	Destabilizing	0.998	D	0.821	deleterious	None	None	None	None	I
I/Q	0.9852	likely_pathogenic	0.988	pathogenic	-1.72	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
I/R	0.9802	likely_pathogenic	0.9835	pathogenic	-1.12	Destabilizing	0.998	D	0.815	deleterious	None	None	None	None	I
I/S	0.967	likely_pathogenic	0.9765	pathogenic	-2.346	Highly Destabilizing	0.991	D	0.774	deleterious	D	0.551848244	None	None	I
I/T	0.9291	likely_pathogenic	0.9316	pathogenic	-2.118	Highly Destabilizing	0.939	D	0.765	deleterious	D	0.531110643	None	None	I
I/V	0.0698	likely_benign	0.0756	benign	-1.457	Destabilizing	0.02	N	0.244	neutral	N	0.491279132	None	None	I
I/W	0.997	likely_pathogenic	0.9979	pathogenic	-1.732	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	I
I/Y	0.9861	likely_pathogenic	0.9897	pathogenic	-1.492	Destabilizing	0.998	D	0.764	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.