TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29345	88258;88259;88260	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
N2AB	27704	83335;83336;83337	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
N2A	26777	80554;80555;80556	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
N2B	20280	61063;61064;61065	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
Novex-1	20405	61438;61439;61440	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
Novex-2	20472	61639;61640;61641	chr2:178557121;178557120;178557119	chr2:179421848;179421847;179421846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-102
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3419
• 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
T/A	rs878854427	None	0.454	N	0.348	0.176	0.214338557667	gnomAD-4.0.0	1.0949E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4392E-05	0	0
T/I	rs1701792162	None	0.051	N	0.25	0.146	0.302793454619	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/I	rs1701792162	None	0.051	N	0.25	0.146	0.302793454619	gnomAD-4.0.0	6.5697E-06	None	None	None	None	N	None	2.41196E-05	0	None	0	0	None	0	0	0	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
T/A	0.1069	likely_benign	0.0964	benign	-0.62	Destabilizing	0.454	N	0.348	neutral	N	0.503456208	None	None	N
T/C	0.4078	ambiguous	0.385	ambiguous	-0.395	Destabilizing	0.998	D	0.399	neutral	None	None	None	None	N
T/D	0.4817	ambiguous	0.4069	ambiguous	0.268	Stabilizing	0.842	D	0.392	neutral	None	None	None	None	N
T/E	0.3828	ambiguous	0.327	benign	0.214	Stabilizing	0.842	D	0.404	neutral	None	None	None	None	N
T/F	0.3373	likely_benign	0.266	benign	-0.99	Destabilizing	0.949	D	0.511	neutral	None	None	None	None	N
T/G	0.2653	likely_benign	0.2377	benign	-0.788	Destabilizing	0.728	D	0.458	neutral	None	None	None	None	N
T/H	0.334	likely_benign	0.2827	benign	-1.073	Destabilizing	0.998	D	0.457	neutral	None	None	None	None	N
T/I	0.1782	likely_benign	0.1536	benign	-0.288	Destabilizing	0.051	N	0.25	neutral	N	0.46351374	None	None	N
T/K	0.2385	likely_benign	0.2096	benign	-0.433	Destabilizing	0.842	D	0.404	neutral	None	None	None	None	N
T/L	0.1149	likely_benign	0.1071	benign	-0.288	Destabilizing	0.016	N	0.207	neutral	None	None	None	None	N
T/M	0.1008	likely_benign	0.0973	benign	-0.041	Destabilizing	0.949	D	0.418	neutral	None	None	None	None	N
T/N	0.1727	likely_benign	0.1508	benign	-0.271	Destabilizing	0.801	D	0.379	neutral	N	0.484450291	None	None	N
T/P	0.3558	ambiguous	0.3184	benign	-0.368	Destabilizing	0.966	D	0.43	neutral	N	0.496731649	None	None	N
T/Q	0.2811	likely_benign	0.2512	benign	-0.495	Destabilizing	0.974	D	0.436	neutral	None	None	None	None	N
T/R	0.1975	likely_benign	0.1675	benign	-0.174	Destabilizing	0.949	D	0.437	neutral	None	None	None	None	N
T/S	0.1341	likely_benign	0.1199	benign	-0.563	Destabilizing	0.022	N	0.125	neutral	N	0.476189462	None	None	N
T/V	0.143	likely_benign	0.1283	benign	-0.368	Destabilizing	0.525	D	0.39	neutral	None	None	None	None	N
T/W	0.6516	likely_pathogenic	0.5745	pathogenic	-0.921	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
T/Y	0.3683	ambiguous	0.3066	benign	-0.667	Destabilizing	0.991	D	0.505	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.