TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33707	101344;101345;101346	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
N2AB	32066	96421;96422;96423	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
N2A	31139	93640;93641;93642	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
N2B	24642	74149;74150;74151	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
Novex-1	24767	74524;74525;74526	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
Novex-2	24834	74725;74726;74727	chr2:178535496;178535495;178535494	chr2:179400223;179400222;179400221
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: Fn3-132
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.3223
• 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/S	rs1691011936	None	0.13	N	0.299	0.117	0.154104182512	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
N/A	0.2592	likely_benign	0.2742	benign	-0.771	Destabilizing	0.252	N	0.479	neutral	None	None	None	None	N
N/C	0.2214	likely_benign	0.2372	benign	-0.248	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
N/D	0.2504	likely_benign	0.2527	benign	-1.438	Destabilizing	0.792	D	0.493	neutral	N	0.471034358	None	None	N
N/E	0.4963	ambiguous	0.5368	ambiguous	-1.344	Destabilizing	0.944	D	0.439	neutral	None	None	None	None	N
N/F	0.4806	ambiguous	0.5119	ambiguous	-0.783	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
N/G	0.4466	ambiguous	0.4563	ambiguous	-1.077	Destabilizing	0.946	D	0.454	neutral	None	None	None	None	N
N/H	0.1053	likely_benign	0.1078	benign	-0.929	Destabilizing	0.997	D	0.459	neutral	N	0.495468656	None	None	N
N/I	0.1539	likely_benign	0.1698	benign	-0.006	Destabilizing	0.984	D	0.572	neutral	N	0.451293804	None	None	N
N/K	0.4343	ambiguous	0.4222	ambiguous	-0.233	Destabilizing	0.979	D	0.441	neutral	N	0.435401632	None	None	N
N/L	0.2119	likely_benign	0.2261	benign	-0.006	Destabilizing	0.959	D	0.509	neutral	None	None	None	None	N
N/M	0.2802	likely_benign	0.3108	benign	0.515	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	N
N/P	0.9255	likely_pathogenic	0.9149	pathogenic	-0.232	Destabilizing	0.973	D	0.551	neutral	None	None	None	None	N
N/Q	0.3775	ambiguous	0.3911	ambiguous	-1.138	Destabilizing	0.994	D	0.451	neutral	None	None	None	None	N
N/R	0.4319	ambiguous	0.4123	ambiguous	-0.152	Destabilizing	0.998	D	0.439	neutral	None	None	None	None	N
N/S	0.0807	likely_benign	0.0836	benign	-0.936	Destabilizing	0.13	N	0.299	neutral	N	0.434284124	None	None	N
N/T	0.0915	likely_benign	0.1029	benign	-0.67	Destabilizing	0.032	N	0.265	neutral	N	0.350012089	None	None	N
N/V	0.167	likely_benign	0.1849	benign	-0.232	Destabilizing	0.663	D	0.509	neutral	None	None	None	None	N
N/W	0.7793	likely_pathogenic	0.7889	pathogenic	-0.612	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
N/Y	0.1622	likely_benign	0.1749	benign	-0.306	Destabilizing	0.999	D	0.566	neutral	N	0.452795314	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.