TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27238	81937;81938;81939	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
N2AB	25597	77014;77015;77016	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
N2A	24670	74233;74234;74235	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
N2B	18173	54742;54743;54744	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
Novex-1	18298	55117;55118;55119	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
Novex-2	18365	55318;55319;55320	chr2:178564420;178564419;178564418	chr2:179429147;179429146;179429145
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-86
• Domain position: 69
• Structural Position: 100
• Q(SASA): 0.5021
• 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
D/Y	None	None	0.093	N	0.594	0.207	0.311079019809	gnomAD-4.0.0	1.36899E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79933E-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
D/A	0.4077	ambiguous	0.3316	benign	-0.374	Destabilizing	0.024	N	0.563	neutral	N	0.472901228	None	None	N
D/C	0.8105	likely_pathogenic	0.7605	pathogenic	-0.063	Destabilizing	0.864	D	0.594	neutral	None	None	None	None	N
D/E	0.2705	likely_benign	0.2429	benign	-0.477	Destabilizing	None	N	0.173	neutral	N	0.448120213	None	None	N
D/F	0.7496	likely_pathogenic	0.6935	pathogenic	-0.332	Destabilizing	0.001	N	0.529	neutral	None	None	None	None	N
D/G	0.1575	likely_benign	0.1267	benign	-0.61	Destabilizing	None	N	0.222	neutral	N	0.355799124	None	None	N
D/H	0.4908	ambiguous	0.4063	ambiguous	-0.407	Destabilizing	0.171	N	0.475	neutral	N	0.51016875	None	None	N
D/I	0.8024	likely_pathogenic	0.7273	pathogenic	0.209	Stabilizing	0.12	N	0.603	neutral	None	None	None	None	N
D/K	0.6982	likely_pathogenic	0.6155	pathogenic	-0.065	Destabilizing	0.038	N	0.457	neutral	None	None	None	None	N
D/L	0.6687	likely_pathogenic	0.5959	pathogenic	0.209	Stabilizing	0.038	N	0.597	neutral	None	None	None	None	N
D/M	0.8102	likely_pathogenic	0.7566	pathogenic	0.438	Stabilizing	0.676	D	0.575	neutral	None	None	None	None	N
D/N	0.0892	likely_benign	0.0734	benign	-0.256	Destabilizing	None	N	0.154	neutral	N	0.41662387	None	None	N
D/P	0.9647	likely_pathogenic	0.9442	pathogenic	0.038	Stabilizing	0.356	N	0.49	neutral	None	None	None	None	N
D/Q	0.5946	likely_pathogenic	0.5204	ambiguous	-0.224	Destabilizing	0.12	N	0.391	neutral	None	None	None	None	N
D/R	0.7385	likely_pathogenic	0.6646	pathogenic	0.101	Stabilizing	0.214	N	0.581	neutral	None	None	None	None	N
D/S	0.2103	likely_benign	0.1687	benign	-0.423	Destabilizing	0.016	N	0.312	neutral	None	None	None	None	N
D/T	0.5359	ambiguous	0.4456	ambiguous	-0.252	Destabilizing	0.038	N	0.439	neutral	None	None	None	None	N
D/V	0.644	likely_pathogenic	0.5704	pathogenic	0.038	Stabilizing	0.055	N	0.571	neutral	N	0.487866878	None	None	N
D/W	0.9361	likely_pathogenic	0.9133	pathogenic	-0.226	Destabilizing	0.864	D	0.604	neutral	None	None	None	None	N
D/Y	0.3418	ambiguous	0.2928	benign	-0.118	Destabilizing	0.093	N	0.594	neutral	N	0.481694069	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.