TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35426	106501;106502;106503	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
N2AB	33785	101578;101579;101580	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
N2A	32858	98797;98798;98799	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
N2B	26361	79306;79307;79308	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
Novex-1	26486	79681;79682;79683	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
Novex-2	26553	79882;79883;79884	chr2:178530339;178530338;178530337	chr2:179395066;179395065;179395064
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-166
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.0986
• 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
L/S	None	None	0.999	N	0.846	0.333	0.782707291019	gnomAD-4.0.0	1.59095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85757E-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
L/A	0.8116	likely_pathogenic	0.8092	pathogenic	-1.881	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
L/C	0.9035	likely_pathogenic	0.8913	pathogenic	-1.496	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
L/D	0.9899	likely_pathogenic	0.9889	pathogenic	-1.052	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
L/E	0.9471	likely_pathogenic	0.9463	pathogenic	-0.997	Destabilizing	0.999	D	0.888	deleterious	None	None	None	None	N
L/F	0.4159	ambiguous	0.4127	ambiguous	-1.35	Destabilizing	0.999	D	0.719	prob.delet.	N	0.46537026	None	None	N
L/G	0.9392	likely_pathogenic	0.9355	pathogenic	-2.253	Highly Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
L/H	0.8952	likely_pathogenic	0.8916	pathogenic	-1.461	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
L/I	0.1961	likely_benign	0.1994	benign	-0.905	Destabilizing	0.998	D	0.561	neutral	None	None	None	None	N
L/K	0.9113	likely_pathogenic	0.913	pathogenic	-1.109	Destabilizing	0.999	D	0.862	deleterious	None	None	None	None	N
L/M	0.269	likely_benign	0.2705	benign	-0.911	Destabilizing	0.999	D	0.743	deleterious	N	0.459369553	None	None	N
L/N	0.9357	likely_pathogenic	0.9308	pathogenic	-1.023	Destabilizing	0.999	D	0.904	deleterious	None	None	None	None	N
L/P	0.8196	likely_pathogenic	0.7898	pathogenic	-1.201	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
L/Q	0.8215	likely_pathogenic	0.8189	pathogenic	-1.142	Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/R	0.8718	likely_pathogenic	0.8724	pathogenic	-0.657	Destabilizing	0.999	D	0.874	deleterious	None	None	None	None	N
L/S	0.9038	likely_pathogenic	0.898	pathogenic	-1.791	Destabilizing	0.999	D	0.846	deleterious	N	0.468915433	None	None	N
L/T	0.8083	likely_pathogenic	0.8061	pathogenic	-1.603	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
L/V	0.3127	likely_benign	0.3176	benign	-1.201	Destabilizing	0.997	D	0.545	neutral	N	0.464863281	None	None	N
L/W	0.8148	likely_pathogenic	0.8201	pathogenic	-1.393	Destabilizing	1.0	D	0.848	deleterious	N	0.506137901	None	None	N
L/Y	0.9058	likely_pathogenic	0.91	pathogenic	-1.14	Destabilizing	0.999	D	0.84	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.