TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21034	63325;63326;63327	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
N2AB	19393	58402;58403;58404	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
N2A	18466	55621;55622;55623	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
N2B	11969	36130;36131;36132	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
Novex-1	12094	36505;36506;36507	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
Novex-2	12161	36706;36707;36708	chr2:178588625;178588624;178588623	chr2:179453352;179453351;179453350
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-40
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0794
• 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
Y/C	None	None	1.0	D	0.862	0.854	0.886387458693	gnomAD-4.0.0	3.26606E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.82992E-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
Y/A	0.9965	likely_pathogenic	0.9956	pathogenic	-3.405	Highly Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
Y/C	0.9553	likely_pathogenic	0.9434	pathogenic	-2.148	Highly Destabilizing	1.0	D	0.862	deleterious	D	0.662024156	None	None	N
Y/D	0.9956	likely_pathogenic	0.9953	pathogenic	-3.843	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.678275682	None	None	N
Y/E	0.9983	likely_pathogenic	0.9981	pathogenic	-3.658	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/F	0.3245	likely_benign	0.3237	benign	-1.346	Destabilizing	0.999	D	0.752	deleterious	D	0.618650445	None	None	N
Y/G	0.991	likely_pathogenic	0.9894	pathogenic	-3.793	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/H	0.986	likely_pathogenic	0.9844	pathogenic	-2.302	Highly Destabilizing	1.0	D	0.829	deleterious	D	0.662024156	None	None	N
Y/I	0.9245	likely_pathogenic	0.9042	pathogenic	-2.101	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
Y/K	0.9986	likely_pathogenic	0.9985	pathogenic	-2.615	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
Y/L	0.941	likely_pathogenic	0.9196	pathogenic	-2.101	Highly Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
Y/M	0.9707	likely_pathogenic	0.9629	pathogenic	-1.779	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
Y/N	0.9691	likely_pathogenic	0.964	pathogenic	-3.368	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.661822352	None	None	N
Y/P	0.9995	likely_pathogenic	0.9994	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.9978	likely_pathogenic	0.9975	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
Y/R	0.9971	likely_pathogenic	0.9965	pathogenic	-2.227	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/S	0.9897	likely_pathogenic	0.9876	pathogenic	-3.682	Highly Destabilizing	1.0	D	0.88	deleterious	D	0.678275682	None	None	N
Y/T	0.9939	likely_pathogenic	0.9919	pathogenic	-3.391	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
Y/V	0.8863	likely_pathogenic	0.853	pathogenic	-2.552	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
Y/W	0.8719	likely_pathogenic	0.8807	pathogenic	-0.712	Destabilizing	1.0	D	0.813	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.