TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29276	88051;88052;88053	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
N2AB	27635	83128;83129;83130	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
N2A	26708	80347;80348;80349	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
N2B	20211	60856;60857;60858	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
Novex-1	20336	61231;61232;61233	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
Novex-2	20403	61432;61433;61434	chr2:178557436;178557435;178557434	chr2:179422163;179422162;179422161
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-101
• Domain position: 40
• Structural Position: 42
• Q(SASA): 0.1249
• 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
M/V	None	None	0.985	N	0.603	0.419	0.46614307118	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
M/A	0.8396	likely_pathogenic	0.7955	pathogenic	-2.271	Highly Destabilizing	0.989	D	0.709	prob.delet.	None	None	None	None	I
M/C	0.7305	likely_pathogenic	0.705	pathogenic	-2.283	Highly Destabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	I
M/D	0.9965	likely_pathogenic	0.9956	pathogenic	-2.127	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	I
M/E	0.9277	likely_pathogenic	0.9065	pathogenic	-1.863	Destabilizing	0.999	D	0.769	deleterious	None	None	None	None	I
M/F	0.4061	ambiguous	0.3833	ambiguous	-0.714	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
M/G	0.945	likely_pathogenic	0.9334	pathogenic	-2.779	Highly Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	I
M/H	0.8311	likely_pathogenic	0.7982	pathogenic	-2.414	Highly Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
M/I	0.5658	likely_pathogenic	0.5275	ambiguous	-0.789	Destabilizing	0.985	D	0.713	prob.delet.	N	0.458777137	None	None	I
M/K	0.3842	ambiguous	0.3937	ambiguous	-1.444	Destabilizing	0.994	D	0.706	prob.neutral	N	0.427704869	None	None	I
M/L	0.2379	likely_benign	0.2484	benign	-0.789	Destabilizing	0.927	D	0.511	neutral	N	0.475071954	None	None	I
M/N	0.9468	likely_pathogenic	0.9311	pathogenic	-1.91	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	I
M/P	0.9988	likely_pathogenic	0.9993	pathogenic	-1.268	Destabilizing	0.999	D	0.783	deleterious	None	None	None	None	I
M/Q	0.5412	ambiguous	0.4985	ambiguous	-1.537	Destabilizing	0.999	D	0.66	neutral	None	None	None	None	I
M/R	0.4492	ambiguous	0.4318	ambiguous	-1.616	Destabilizing	0.998	D	0.715	prob.delet.	N	0.371928944	None	None	I
M/S	0.8918	likely_pathogenic	0.8544	pathogenic	-2.46	Highly Destabilizing	0.995	D	0.7	prob.neutral	None	None	None	None	I
M/T	0.7309	likely_pathogenic	0.6722	pathogenic	-2.063	Highly Destabilizing	0.994	D	0.701	prob.neutral	N	0.495660657	None	None	I
M/V	0.1865	likely_benign	0.1753	benign	-1.268	Destabilizing	0.985	D	0.603	neutral	N	0.462950806	None	None	I
M/W	0.7535	likely_pathogenic	0.7636	pathogenic	-1.072	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
M/Y	0.6258	likely_pathogenic	0.6087	pathogenic	-1.057	Destabilizing	0.999	D	0.73	prob.delet.	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.