TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18898	56917;56918;56919	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
N2AB	17257	51994;51995;51996	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
N2A	16330	49213;49214;49215	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
N2B	9833	29722;29723;29724	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
Novex-1	9958	30097;30098;30099	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
Novex-2	10025	30298;30299;30300	chr2:178599018;178599017;178599016	chr2:179463745;179463744;179463743
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGT
• RefSeq wild type template codon: GCA
• Domain: Fn3-25
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4662
• 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
R/C	rs893885472	-0.71	0.999	N	0.48	0.348	0.574775486166	gnomAD-2.1.1	1.12E-05	None	None	None	None	N	None	4.22E-05	0	None	0	0	None	0	None	0	8.16E-06	1.48192E-04
R/C	rs893885472	-0.71	0.999	N	0.48	0.348	0.574775486166	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
R/C	rs893885472	-0.71	0.999	N	0.48	0.348	0.574775486166	gnomAD-4.0.0	6.88541E-06	None	None	None	None	N	None	1.34742E-05	1.72408E-05	None	0	2.25887E-05	None	0	0	5.12297E-06	1.12651E-05	1.61996E-05
R/G	None	None	0.485	N	0.451	0.234	0.364926071151	gnomAD-4.0.0	6.91713E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	1.75747E-04	0	0	0
R/H	rs572453785	-1.262	0.031	N	0.203	0.104	None	gnomAD-2.1.1	5.22E-05	None	None	None	None	N	None	1.68535E-04	3.02E-05	None	0	1.0591E-04	None	6.99E-05	None	0	4.07E-05	0
R/H	rs572453785	-1.262	0.031	N	0.203	0.104	None	gnomAD-3.1.2	1.11922E-04	None	None	None	None	N	None	2.65855E-04	6.56E-05	0	0	1.94628E-04	None	0	0	4.42E-05	2.07727E-04	0
R/H	rs572453785	-1.262	0.031	N	0.203	0.104	None	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	1.4E-03	None	None	0	0	None	None	None	0	None
R/H	rs572453785	-1.262	0.031	N	0.203	0.104	None	gnomAD-4.0.0	8.25614E-05	None	None	None	None	N	None	2.68918E-04	5.14845E-05	None	0	6.77629E-05	None	0	1.67001E-04	7.42506E-05	8.99726E-05	1.61818E-04

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
R/A	0.3728	ambiguous	0.3508	ambiguous	-0.445	Destabilizing	0.004	N	0.137	neutral	None	None	None	None	N
R/C	0.1593	likely_benign	0.1949	benign	-0.306	Destabilizing	0.999	D	0.48	neutral	N	0.485118173	None	None	N
R/D	0.7911	likely_pathogenic	0.7832	pathogenic	-0.263	Destabilizing	0.704	D	0.484	neutral	None	None	None	None	N
R/E	0.4767	ambiguous	0.4373	ambiguous	-0.196	Destabilizing	0.704	D	0.214	neutral	None	None	None	None	N
R/F	0.6818	likely_pathogenic	0.673	pathogenic	-0.611	Destabilizing	0.893	D	0.531	neutral	None	None	None	None	N
R/G	0.2609	likely_benign	0.2696	benign	-0.685	Destabilizing	0.485	N	0.451	neutral	N	0.45329396	None	None	N
R/H	0.1083	likely_benign	0.1163	benign	-1.117	Destabilizing	0.031	N	0.203	neutral	N	0.462414875	None	None	N
R/I	0.4637	ambiguous	0.4616	ambiguous	0.173	Stabilizing	0.543	D	0.533	neutral	None	None	None	None	N
R/K	0.1144	likely_benign	0.1082	benign	-0.527	Destabilizing	0.495	N	0.255	neutral	None	None	None	None	N
R/L	0.3597	ambiguous	0.3609	ambiguous	0.173	Stabilizing	0.006	N	0.161	neutral	N	0.499759755	None	None	N
R/M	0.3933	ambiguous	0.3839	ambiguous	0.034	Stabilizing	0.893	D	0.423	neutral	None	None	None	None	N
R/N	0.6077	likely_pathogenic	0.5853	pathogenic	0.024	Stabilizing	0.704	D	0.298	neutral	None	None	None	None	N
R/P	0.7285	likely_pathogenic	0.7395	pathogenic	-0.013	Destabilizing	0.97	D	0.487	neutral	N	0.452061809	None	None	N
R/Q	0.1098	likely_benign	0.1151	benign	-0.235	Destabilizing	0.704	D	0.321	neutral	None	None	None	None	N
R/S	0.4614	ambiguous	0.4427	ambiguous	-0.534	Destabilizing	0.485	N	0.377	neutral	N	0.432569184	None	None	N
R/T	0.4211	ambiguous	0.3934	ambiguous	-0.323	Destabilizing	0.704	D	0.377	neutral	None	None	None	None	N
R/V	0.5083	ambiguous	0.5098	ambiguous	-0.013	Destabilizing	0.329	N	0.491	neutral	None	None	None	None	N
R/W	0.2721	likely_benign	0.3063	benign	-0.449	Destabilizing	0.995	D	0.486	neutral	None	None	None	None	N
R/Y	0.4434	ambiguous	0.4438	ambiguous	-0.086	Destabilizing	0.893	D	0.489	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.