TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9555	28888;28889;28890	chr2:178709656;178709655;178709654	chr2:179574383;179574382;179574381
N2AB	9238	27937;27938;27939	chr2:178709656;178709655;178709654	chr2:179574383;179574382;179574381
N2A	8311	25156;25157;25158	chr2:178709656;178709655;178709654	chr2:179574383;179574382;179574381
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: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-81
• Domain position: 63
• Structural Position: 143
• Q(SASA): 0.3128
• 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
K/T	rs760060633	-0.028	0.001	None	0.193	0.076	0.12205267543	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/T	rs760060633	-0.028	0.001	None	0.193	0.076	0.12205267543	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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
K/A	0.2352	likely_benign	0.2328	benign	-0.028	Destabilizing	0.016	N	0.36	neutral	None	None	None	None	N
K/C	0.5775	likely_pathogenic	0.5718	pathogenic	-0.147	Destabilizing	0.864	D	0.392	neutral	None	None	None	None	N
K/D	0.3145	likely_benign	0.3076	benign	0.162	Stabilizing	0.038	N	0.335	neutral	None	None	None	None	N
K/E	0.1157	likely_benign	0.1064	benign	0.162	Stabilizing	0.012	N	0.293	neutral	None	None	None	None	N
K/F	0.6428	likely_pathogenic	0.6017	pathogenic	-0.294	Destabilizing	0.356	N	0.414	neutral	None	None	None	None	N
K/G	0.2852	likely_benign	0.2715	benign	-0.225	Destabilizing	0.016	N	0.345	neutral	None	None	None	None	N
K/H	0.214	likely_benign	0.2097	benign	-0.571	Destabilizing	0.356	N	0.366	neutral	None	None	None	None	N
K/I	0.3116	likely_benign	0.2891	benign	0.407	Stabilizing	0.171	N	0.433	neutral	None	None	None	None	N
K/L	0.2951	likely_benign	0.2755	benign	0.407	Stabilizing	0.038	N	0.377	neutral	None	None	None	None	N
K/M	0.177	likely_benign	0.1712	benign	0.344	Stabilizing	0.628	D	0.367	neutral	None	None	None	None	N
K/N	0.1888	likely_benign	0.1858	benign	0.309	Stabilizing	None	N	0.095	neutral	None	None	None	None	N
K/P	0.7825	likely_pathogenic	0.7365	pathogenic	0.29	Stabilizing	0.356	N	0.396	neutral	None	None	None	None	N
K/Q	0.1031	likely_benign	0.0986	benign	0.087	Stabilizing	0.055	N	0.348	neutral	None	None	None	None	N
K/R	0.0798	likely_benign	0.0761	benign	0.039	Stabilizing	None	N	0.233	neutral	None	None	None	None	N
K/S	0.2363	likely_benign	0.2328	benign	-0.23	Destabilizing	None	N	0.089	neutral	None	None	None	None	N
K/T	0.1349	likely_benign	0.1339	benign	-0.081	Destabilizing	0.001	N	0.193	neutral	None	None	None	None	N
K/V	0.2857	likely_benign	0.2773	benign	0.29	Stabilizing	0.038	N	0.394	neutral	None	None	None	None	N
K/W	0.6475	likely_pathogenic	0.5971	pathogenic	-0.277	Destabilizing	0.864	D	0.449	neutral	None	None	None	None	N
K/Y	0.4659	ambiguous	0.4287	ambiguous	0.091	Stabilizing	0.356	N	0.393	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.