TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9537	28834;28835;28836	chr2:178709710;178709709;178709708	chr2:179574437;179574436;179574435
N2AB	9220	27883;27884;27885	chr2:178709710;178709709;178709708	chr2:179574437;179574436;179574435
N2A	8293	25102;25103;25104	chr2:178709710;178709709;178709708	chr2:179574437;179574436;179574435
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-81
• Domain position: 45
• Structural Position: 73
• Q(SASA): 0.6364
• 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
T/I	None	None	0.627	None	0.333	0.101	0.311387274539	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.0817	likely_benign	0.0817	benign	-0.303	Destabilizing	0.041	N	0.196	neutral	None	None	None	None	N
T/C	0.4666	ambiguous	0.4441	ambiguous	-0.174	Destabilizing	0.944	D	0.275	neutral	None	None	None	None	N
T/D	0.2559	likely_benign	0.2234	benign	-0.02	Destabilizing	0.388	N	0.296	neutral	None	None	None	None	N
T/E	0.3517	ambiguous	0.3148	benign	-0.112	Destabilizing	0.241	N	0.288	neutral	None	None	None	None	N
T/F	0.3202	likely_benign	0.2678	benign	-0.906	Destabilizing	0.818	D	0.349	neutral	None	None	None	None	N
T/G	0.1558	likely_benign	0.1553	benign	-0.396	Destabilizing	0.001	N	0.162	neutral	None	None	None	None	N
T/H	0.289	likely_benign	0.2497	benign	-0.722	Destabilizing	0.818	D	0.321	neutral	None	None	None	None	N
T/I	0.3075	likely_benign	0.2499	benign	-0.178	Destabilizing	0.627	D	0.333	neutral	None	None	None	None	N
T/K	0.3192	likely_benign	0.2646	benign	-0.341	Destabilizing	0.241	N	0.287	neutral	None	None	None	None	N
T/L	0.1472	likely_benign	0.1329	benign	-0.178	Destabilizing	0.388	N	0.297	neutral	None	None	None	None	N
T/M	0.1487	likely_benign	0.1291	benign	0.04	Stabilizing	0.932	D	0.275	neutral	None	None	None	None	N
T/N	0.0992	likely_benign	0.0969	benign	-0.074	Destabilizing	0.193	N	0.245	neutral	None	None	None	None	N
T/P	0.384	ambiguous	0.3576	ambiguous	-0.193	Destabilizing	0.492	N	0.324	neutral	None	None	None	None	N
T/Q	0.2933	likely_benign	0.2602	benign	-0.329	Destabilizing	0.69	D	0.319	neutral	None	None	None	None	N
T/R	0.2517	likely_benign	0.2037	benign	-0.061	Destabilizing	0.388	N	0.343	neutral	None	None	None	None	N
T/S	0.0703	likely_benign	0.0737	benign	-0.235	Destabilizing	None	N	0.105	neutral	None	None	None	None	N
T/V	0.2085	likely_benign	0.1817	benign	-0.193	Destabilizing	0.388	N	0.228	neutral	None	None	None	None	N
T/W	0.7512	likely_pathogenic	0.6616	pathogenic	-0.947	Destabilizing	0.981	D	0.337	neutral	None	None	None	None	N
T/Y	0.3888	ambiguous	0.327	benign	-0.649	Destabilizing	0.818	D	0.337	neutral	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.