TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17882	53869;53870;53871	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
N2AB	16241	48946;48947;48948	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
N2A	15314	46165;46166;46167	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
N2B	8817	26674;26675;26676	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
Novex-1	8942	27049;27050;27051	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
Novex-2	9009	27250;27251;27252	chr2:178605651;178605650;178605649	chr2:179470378;179470377;179470376
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: Fn3-18
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.3563
• 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/N	None	None	0.959	N	0.397	0.133	0.209622950755	gnomAD-4.0.0	4.79926E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.62589E-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	0.4023	ambiguous	0.3905	ambiguous	-0.969	Destabilizing	0.061	N	0.438	neutral	N	0.379297633	None	None	N
D/C	0.8521	likely_pathogenic	0.8496	pathogenic	-0.436	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	N
D/E	0.3317	likely_benign	0.3182	benign	-0.775	Destabilizing	0.134	N	0.185	neutral	N	0.401787704	None	None	N
D/F	0.8151	likely_pathogenic	0.8001	pathogenic	-0.918	Destabilizing	0.997	D	0.609	neutral	None	None	None	None	N
D/G	0.5558	ambiguous	0.5307	ambiguous	-1.314	Destabilizing	0.826	D	0.441	neutral	N	0.426686148	None	None	N
D/H	0.5352	ambiguous	0.5256	ambiguous	-1.133	Destabilizing	0.996	D	0.547	neutral	N	0.425608713	None	None	N
D/I	0.6631	likely_pathogenic	0.6436	pathogenic	-0.045	Destabilizing	0.982	D	0.605	neutral	None	None	None	None	N
D/K	0.7861	likely_pathogenic	0.7809	pathogenic	-0.561	Destabilizing	0.884	D	0.449	neutral	None	None	None	None	N
D/L	0.6227	likely_pathogenic	0.6118	pathogenic	-0.045	Destabilizing	0.939	D	0.507	neutral	None	None	None	None	N
D/M	0.825	likely_pathogenic	0.8031	pathogenic	0.552	Stabilizing	0.999	D	0.601	neutral	None	None	None	None	N
D/N	0.23	likely_benign	0.2229	benign	-0.89	Destabilizing	0.959	D	0.397	neutral	N	0.443423683	None	None	N
D/P	0.9944	likely_pathogenic	0.9938	pathogenic	-0.33	Destabilizing	0.991	D	0.535	neutral	None	None	None	None	N
D/Q	0.6135	likely_pathogenic	0.5838	pathogenic	-0.764	Destabilizing	0.939	D	0.461	neutral	None	None	None	None	N
D/R	0.7634	likely_pathogenic	0.7537	pathogenic	-0.524	Destabilizing	0.046	N	0.484	neutral	None	None	None	None	N
D/S	0.2937	likely_benign	0.2768	benign	-1.303	Destabilizing	0.759	D	0.426	neutral	None	None	None	None	N
D/T	0.4458	ambiguous	0.4332	ambiguous	-0.996	Destabilizing	0.17	N	0.307	neutral	None	None	None	None	N
D/V	0.4818	ambiguous	0.4558	ambiguous	-0.33	Destabilizing	0.92	D	0.505	neutral	N	0.441212884	None	None	N
D/W	0.9645	likely_pathogenic	0.9594	pathogenic	-0.81	Destabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
D/Y	0.5184	ambiguous	0.512	ambiguous	-0.663	Destabilizing	0.996	D	0.605	neutral	N	0.497412883	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.