TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14324	43195;43196;43197	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
N2AB	12683	38272;38273;38274	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
N2A	11756	35491;35492;35493	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
N2B	5259	16000;16001;16002	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
Novex-1	5384	16375;16376;16377	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
Novex-2	5451	16576;16577;16578	chr2:178633303;178633302;178633301	chr2:179498030;179498029;179498028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-94
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.3663
• 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
P/T	None	None	1.0	N	0.801	0.419	0.360565625551	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.2286	likely_benign	0.22	benign	-1.048	Destabilizing	0.999	D	0.802	deleterious	N	0.520589675	None	None	N
P/C	0.8902	likely_pathogenic	0.8864	pathogenic	-0.699	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
P/D	0.8246	likely_pathogenic	0.7968	pathogenic	-0.583	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/E	0.6655	likely_pathogenic	0.6392	pathogenic	-0.559	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
P/F	0.8825	likely_pathogenic	0.8836	pathogenic	-0.661	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
P/G	0.6591	likely_pathogenic	0.5985	pathogenic	-1.363	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/H	0.5447	ambiguous	0.559	ambiguous	-0.804	Destabilizing	1.0	D	0.788	deleterious	N	0.466195377	None	None	N
P/I	0.7673	likely_pathogenic	0.7753	pathogenic	-0.291	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/K	0.6723	likely_pathogenic	0.6507	pathogenic	-0.85	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/L	0.398	ambiguous	0.3901	ambiguous	-0.291	Destabilizing	1.0	D	0.863	deleterious	N	0.521362072	None	None	N
P/M	0.7247	likely_pathogenic	0.721	pathogenic	-0.334	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/N	0.7321	likely_pathogenic	0.7135	pathogenic	-0.75	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/Q	0.4515	ambiguous	0.4486	ambiguous	-0.834	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/R	0.494	ambiguous	0.4948	ambiguous	-0.434	Destabilizing	1.0	D	0.859	deleterious	N	0.481026843	None	None	N
P/S	0.4079	ambiguous	0.3787	ambiguous	-1.291	Destabilizing	1.0	D	0.821	deleterious	D	0.542114786	None	None	N
P/T	0.3667	ambiguous	0.366	ambiguous	-1.15	Destabilizing	1.0	D	0.801	deleterious	N	0.520589675	None	None	N
P/V	0.6191	likely_pathogenic	0.6267	pathogenic	-0.508	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/W	0.944	likely_pathogenic	0.9452	pathogenic	-0.883	Destabilizing	1.0	D	0.703	prob.delet.	None	None	None	None	N
P/Y	0.827	likely_pathogenic	0.8276	pathogenic	-0.545	Destabilizing	1.0	D	0.844	deleterious	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.