TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6683	20272;20273;20274	chr2:178727318;178727317;178727316	chr2:179592045;179592044;179592043
N2AB	6366	19321;19322;19323	chr2:178727318;178727317;178727316	chr2:179592045;179592044;179592043
N2A	5439	16540;16541;16542	chr2:178727318;178727317;178727316	chr2:179592045;179592044;179592043
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-51
• Domain position: 17
• Structural Position: 25
• Q(SASA): 0.3128
• 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/E	None	None	0.619	N	0.259	0.083	0.198526703765	gnomAD-4.0.0	1.5972E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86847E-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	0.2448	likely_benign	0.2597	benign	-0.403	Destabilizing	0.992	D	0.611	neutral	N	0.495209579	None	None	N
D/C	0.7589	likely_pathogenic	0.7743	pathogenic	0.135	Stabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
D/E	0.1649	likely_benign	0.1604	benign	-0.337	Destabilizing	0.619	D	0.259	neutral	N	0.419842242	None	None	N
D/F	0.6107	likely_pathogenic	0.6165	pathogenic	-0.415	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/G	0.274	likely_benign	0.2927	benign	-0.609	Destabilizing	0.996	D	0.629	neutral	N	0.459960855	None	None	N
D/H	0.432	ambiguous	0.4716	ambiguous	-0.446	Destabilizing	1.0	D	0.755	deleterious	N	0.465379806	None	None	N
D/I	0.4673	ambiguous	0.4624	ambiguous	0.098	Stabilizing	1.0	D	0.79	deleterious	None	None	None	None	N
D/K	0.5623	ambiguous	0.5885	pathogenic	0.321	Stabilizing	0.998	D	0.687	prob.neutral	None	None	None	None	N
D/L	0.5167	ambiguous	0.5303	ambiguous	0.098	Stabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
D/M	0.6772	likely_pathogenic	0.6825	pathogenic	0.409	Stabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
D/N	0.1302	likely_benign	0.1366	benign	0.021	Stabilizing	0.999	D	0.707	prob.neutral	N	0.512640547	None	None	N
D/P	0.9476	likely_pathogenic	0.9536	pathogenic	-0.047	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
D/Q	0.402	ambiguous	0.4255	ambiguous	0.049	Stabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
D/R	0.6282	likely_pathogenic	0.6629	pathogenic	0.369	Stabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
D/S	0.1631	likely_benign	0.1724	benign	-0.092	Destabilizing	0.994	D	0.6	neutral	None	None	None	None	N
D/T	0.334	likely_benign	0.3349	benign	0.073	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
D/V	0.302	likely_benign	0.2992	benign	-0.047	Destabilizing	0.999	D	0.758	deleterious	N	0.475356986	None	None	N
D/W	0.9362	likely_pathogenic	0.9399	pathogenic	-0.284	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
D/Y	0.3036	likely_benign	0.3267	benign	-0.177	Destabilizing	1.0	D	0.79	deleterious	N	0.465886785	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.