TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20097	60514;60515;60516	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
N2AB	18456	55591;55592;55593	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
N2A	17529	52810;52811;52812	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
N2B	11032	33319;33320;33321	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
Novex-1	11157	33694;33695;33696	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
Novex-2	11224	33895;33896;33897	chr2:178591436;178591435;178591434	chr2:179456163;179456162;179456161
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-120
• Domain position: 18
• Structural Position: 29
• Q(SASA): 0.7001
• 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/K	None	None	0.997	N	0.545	0.27	0.211220785272	gnomAD-4.0.0	1.61338E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88869E-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
R/A	0.6184	likely_pathogenic	0.6273	pathogenic	-0.464	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
R/C	0.2082	likely_benign	0.2036	benign	-0.539	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
R/D	0.8346	likely_pathogenic	0.8208	pathogenic	0.073	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/E	0.5723	likely_pathogenic	0.5449	ambiguous	0.205	Stabilizing	0.999	D	0.654	neutral	None	None	None	None	N
R/F	0.7173	likely_pathogenic	0.7106	pathogenic	-0.3	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
R/G	0.5756	likely_pathogenic	0.5869	pathogenic	-0.77	Destabilizing	1.0	D	0.683	prob.neutral	N	0.485495069	None	None	N
R/H	0.1159	likely_benign	0.1094	benign	-1.124	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
R/I	0.3119	likely_benign	0.299	benign	0.346	Stabilizing	1.0	D	0.741	deleterious	N	0.504172992	None	None	N
R/K	0.1425	likely_benign	0.1313	benign	-0.453	Destabilizing	0.997	D	0.545	neutral	N	0.450666581	None	None	N
R/L	0.3544	ambiguous	0.3562	ambiguous	0.346	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
R/M	0.4055	ambiguous	0.3978	ambiguous	-0.169	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
R/N	0.6883	likely_pathogenic	0.6728	pathogenic	-0.13	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
R/P	0.9275	likely_pathogenic	0.9252	pathogenic	0.098	Stabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/Q	0.1377	likely_benign	0.1337	benign	-0.199	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
R/S	0.6015	likely_pathogenic	0.6065	pathogenic	-0.769	Destabilizing	1.0	D	0.718	prob.delet.	N	0.495361508	None	None	N
R/T	0.2875	likely_benign	0.2806	benign	-0.451	Destabilizing	1.0	D	0.713	prob.delet.	N	0.439177364	None	None	N
R/V	0.385	ambiguous	0.3779	ambiguous	0.098	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/W	0.3116	likely_benign	0.3022	benign	-0.069	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
R/Y	0.5255	ambiguous	0.4943	ambiguous	0.252	Stabilizing	1.0	D	0.739	prob.delet.	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.