TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29306	88141;88142;88143	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
N2AB	27665	83218;83219;83220	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
N2A	26738	80437;80438;80439	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
N2B	20241	60946;60947;60948	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
Novex-1	20366	61321;61322;61323	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
Novex-2	20433	61522;61523;61524	chr2:178557346;178557345;178557344	chr2:179422073;179422072;179422071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-101
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.3576
• Predicted PPI site: I

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/F	rs551887772	-0.927	1.0	N	0.683	0.363	0.534140917371	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	1E-03	None	None	None	0	None
L/V	None	None	0.999	N	0.418	0.28	0.465549362696	gnomAD-4.0.0	1.59101E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43271E-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
L/A	0.7277	likely_pathogenic	0.768	pathogenic	-1.74	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	I
L/C	0.7542	likely_pathogenic	0.7739	pathogenic	-0.912	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
L/D	0.964	likely_pathogenic	0.9687	pathogenic	-0.889	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
L/E	0.8537	likely_pathogenic	0.8682	pathogenic	-0.835	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
L/F	0.4745	ambiguous	0.4875	ambiguous	-1.131	Destabilizing	1.0	D	0.683	prob.neutral	N	0.475229899	None	None	I
L/G	0.8814	likely_pathogenic	0.9046	pathogenic	-2.117	Highly Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
L/H	0.637	likely_pathogenic	0.6672	pathogenic	-1.318	Destabilizing	1.0	D	0.68	prob.neutral	N	0.476690894	None	None	I
L/I	0.2255	likely_benign	0.2356	benign	-0.754	Destabilizing	0.999	D	0.453	neutral	N	0.436017708	None	None	I
L/K	0.7068	likely_pathogenic	0.7426	pathogenic	-1.031	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
L/M	0.1904	likely_benign	0.2068	benign	-0.532	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I
L/N	0.6815	likely_pathogenic	0.7049	pathogenic	-0.908	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
L/P	0.9896	likely_pathogenic	0.9905	pathogenic	-1.052	Destabilizing	1.0	D	0.696	prob.neutral	N	0.481724359	None	None	I
L/Q	0.458	ambiguous	0.4962	ambiguous	-1.003	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
L/R	0.6077	likely_pathogenic	0.6439	pathogenic	-0.548	Destabilizing	1.0	D	0.708	prob.delet.	N	0.484403514	None	None	I
L/S	0.7838	likely_pathogenic	0.8227	pathogenic	-1.628	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
L/T	0.6919	likely_pathogenic	0.7363	pathogenic	-1.449	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
L/V	0.2805	likely_benign	0.3052	benign	-1.052	Destabilizing	0.999	D	0.418	neutral	N	0.459489213	None	None	I
L/W	0.7524	likely_pathogenic	0.7518	pathogenic	-1.257	Destabilizing	1.0	D	0.67	neutral	None	None	None	None	I
L/Y	0.7296	likely_pathogenic	0.7383	pathogenic	-1.001	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I

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.