TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29220	87883;87884;87885	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
N2AB	27579	82960;82961;82962	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
N2A	26652	80179;80180;80181	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
N2B	20155	60688;60689;60690	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
Novex-1	20280	61063;61064;61065	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
Novex-2	20347	61264;61265;61266	chr2:178557696;178557695;178557694	chr2:179422423;179422422;179422421
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-100
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.2335
• 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
I/V	rs1553554246	None	0.043	N	0.365	0.119	0.441844919209	gnomAD-4.0.0	1.36833E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99423E-07	0	1.65645E-05

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
I/A	0.5204	ambiguous	0.5868	pathogenic	-1.376	Destabilizing	0.25	N	0.593	neutral	None	None	None	None	N
I/C	0.6734	likely_pathogenic	0.7273	pathogenic	-0.961	Destabilizing	0.947	D	0.712	prob.delet.	None	None	None	None	N
I/D	0.8549	likely_pathogenic	0.9086	pathogenic	-0.401	Destabilizing	0.7	D	0.767	deleterious	None	None	None	None	N
I/E	0.7162	likely_pathogenic	0.8019	pathogenic	-0.433	Destabilizing	0.7	D	0.766	deleterious	None	None	None	None	N
I/F	0.2075	likely_benign	0.2648	benign	-1.013	Destabilizing	0.781	D	0.683	prob.neutral	N	0.482093927	None	None	N
I/G	0.8158	likely_pathogenic	0.8623	pathogenic	-1.643	Destabilizing	0.7	D	0.753	deleterious	None	None	None	None	N
I/H	0.646	likely_pathogenic	0.7271	pathogenic	-0.681	Destabilizing	0.982	D	0.777	deleterious	None	None	None	None	N
I/K	0.527	ambiguous	0.6053	pathogenic	-0.719	Destabilizing	0.7	D	0.768	deleterious	None	None	None	None	N
I/L	0.1488	likely_benign	0.1578	benign	-0.746	Destabilizing	0.094	N	0.395	neutral	N	0.44980815	None	None	N
I/M	0.144	likely_benign	0.1627	benign	-0.647	Destabilizing	0.781	D	0.648	neutral	N	0.474629237	None	None	N
I/N	0.4294	ambiguous	0.5215	ambiguous	-0.508	Destabilizing	0.638	D	0.782	deleterious	N	0.490886769	None	None	N
I/P	0.8722	likely_pathogenic	0.8814	pathogenic	-0.923	Destabilizing	0.826	D	0.789	deleterious	None	None	None	None	N
I/Q	0.57	likely_pathogenic	0.6581	pathogenic	-0.731	Destabilizing	0.826	D	0.779	deleterious	None	None	None	None	N
I/R	0.4721	ambiguous	0.553	ambiguous	-0.102	Destabilizing	0.7	D	0.785	deleterious	None	None	None	None	N
I/S	0.459	ambiguous	0.5283	ambiguous	-1.176	Destabilizing	0.201	N	0.652	neutral	N	0.481131135	None	None	N
I/T	0.3372	likely_benign	0.402	ambiguous	-1.09	Destabilizing	0.002	N	0.339	neutral	N	0.458504991	None	None	N
I/V	0.0767	likely_benign	0.0836	benign	-0.923	Destabilizing	0.043	N	0.365	neutral	N	0.415503576	None	None	N
I/W	0.864	likely_pathogenic	0.895	pathogenic	-0.958	Destabilizing	0.982	D	0.771	deleterious	None	None	None	None	N
I/Y	0.6048	likely_pathogenic	0.6778	pathogenic	-0.751	Destabilizing	0.826	D	0.734	prob.delet.	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.