TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6813	20662;20663;20664	chr2:178725885;178725884;178725883	chr2:179590612;179590611;179590610
N2AB	6496	19711;19712;19713	chr2:178725885;178725884;178725883	chr2:179590612;179590611;179590610
N2A	5569	16930;16931;16932	chr2:178725885;178725884;178725883	chr2:179590612;179590611;179590610
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-52
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.4852
• 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
N/H	None	None	0.006	N	0.137	0.114	0.168933306366	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86049E-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
N/A	0.3805	ambiguous	0.2941	benign	-0.652	Destabilizing	0.015	N	0.268	neutral	None	None	None	None	N
N/C	0.6078	likely_pathogenic	0.5428	ambiguous	-0.076	Destabilizing	0.985	D	0.324	neutral	None	None	None	None	N
N/D	0.1625	likely_benign	0.1254	benign	-0.017	Destabilizing	0.001	N	0.112	neutral	N	0.500829696	None	None	N
N/E	0.5256	ambiguous	0.4231	ambiguous	0.053	Stabilizing	0.135	N	0.191	neutral	None	None	None	None	N
N/F	0.647	likely_pathogenic	0.5761	pathogenic	-0.806	Destabilizing	0.953	D	0.337	neutral	None	None	None	None	N
N/G	0.3758	ambiguous	0.2988	benign	-0.904	Destabilizing	0.003	N	0.104	neutral	None	None	None	None	N
N/H	0.1757	likely_benign	0.1492	benign	-0.633	Destabilizing	0.006	N	0.137	neutral	N	0.484073395	None	None	N
N/I	0.3648	ambiguous	0.3005	benign	-0.041	Destabilizing	0.851	D	0.357	neutral	N	0.512470772	None	None	N
N/K	0.4848	ambiguous	0.4288	ambiguous	-0.012	Destabilizing	0.307	N	0.174	neutral	N	0.503870001	None	None	N
N/L	0.3717	ambiguous	0.3332	benign	-0.041	Destabilizing	0.515	D	0.293	neutral	None	None	None	None	N
N/M	0.4673	ambiguous	0.4041	ambiguous	-0.055	Destabilizing	0.958	D	0.303	neutral	None	None	None	None	N
N/P	0.7223	likely_pathogenic	0.6264	pathogenic	-0.218	Destabilizing	0.618	D	0.361	neutral	None	None	None	None	N
N/Q	0.4684	ambiguous	0.3859	ambiguous	-0.446	Destabilizing	0.014	N	0.097	neutral	None	None	None	None	N
N/R	0.5453	ambiguous	0.5063	ambiguous	-0.007	Destabilizing	0.009	N	0.137	neutral	None	None	None	None	N
N/S	0.1515	likely_benign	0.1238	benign	-0.543	Destabilizing	0.067	N	0.236	neutral	D	0.522898479	None	None	N
N/T	0.2433	likely_benign	0.186	benign	-0.296	Destabilizing	0.21	N	0.135	neutral	D	0.529787166	None	None	N
N/V	0.4085	ambiguous	0.335	benign	-0.218	Destabilizing	0.153	N	0.327	neutral	None	None	None	None	N
N/W	0.8773	likely_pathogenic	0.8393	pathogenic	-0.743	Destabilizing	0.996	D	0.344	neutral	None	None	None	None	N
N/Y	0.2049	likely_benign	0.1832	benign	-0.455	Destabilizing	0.882	D	0.345	neutral	N	0.494873496	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.