TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14802	44629;44630;44631	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
N2AB	13161	39706;39707;39708	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
N2A	12234	36925;36926;36927	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
N2B	5737	17434;17435;17436	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
Novex-1	5862	17809;17810;17811	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
Novex-2	5929	18010;18011;18012	chr2:178629321;178629320;178629319	chr2:179494048;179494047;179494046
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-99
• Domain position: 38
• Structural Position: 56
• Q(SASA): 0.5015
• 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/E	None	None	0.992	N	0.52	0.347	0.371718192555	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
K/A	0.3651	ambiguous	0.4531	ambiguous	-0.47	Destabilizing	0.997	D	0.585	neutral	None	None	None	None	N
K/C	0.679	likely_pathogenic	0.7379	pathogenic	-0.479	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
K/D	0.7803	likely_pathogenic	0.8675	pathogenic	-0.111	Destabilizing	0.999	D	0.648	neutral	None	None	None	None	N
K/E	0.265	likely_benign	0.3354	benign	0.015	Stabilizing	0.992	D	0.52	neutral	N	0.479078255	None	None	N
K/F	0.7525	likely_pathogenic	0.848	pathogenic	-0.027	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
K/G	0.6327	likely_pathogenic	0.7272	pathogenic	-0.834	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/H	0.392	ambiguous	0.475	ambiguous	-1.009	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	N
K/I	0.2208	likely_benign	0.2951	benign	0.476	Stabilizing	1.0	D	0.718	prob.delet.	N	0.507898426	None	None	N
K/L	0.2304	likely_benign	0.2897	benign	0.476	Stabilizing	1.0	D	0.593	neutral	None	None	None	None	N
K/M	0.1538	likely_benign	0.2012	benign	0.102	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/N	0.4981	ambiguous	0.628	pathogenic	-0.456	Destabilizing	0.999	D	0.634	neutral	N	0.504244797	None	None	N
K/P	0.4328	ambiguous	0.5001	ambiguous	0.19	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/Q	0.1604	likely_benign	0.1892	benign	-0.427	Destabilizing	0.957	D	0.294	neutral	N	0.495996007	None	None	N
K/R	0.104	likely_benign	0.1102	benign	-0.547	Destabilizing	0.996	D	0.527	neutral	N	0.493765252	None	None	N
K/S	0.5773	likely_pathogenic	0.6934	pathogenic	-1.007	Destabilizing	0.997	D	0.575	neutral	None	None	None	None	N
K/T	0.2252	likely_benign	0.3198	benign	-0.681	Destabilizing	0.999	D	0.657	neutral	N	0.506083591	None	None	N
K/V	0.2488	likely_benign	0.3181	benign	0.19	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
K/W	0.8093	likely_pathogenic	0.8686	pathogenic	0.021	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/Y	0.6396	likely_pathogenic	0.7278	pathogenic	0.282	Stabilizing	1.0	D	0.695	prob.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.