TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29301	88126;88127;88128	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
N2AB	27660	83203;83204;83205	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
N2A	26733	80422;80423;80424	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
N2B	20236	60931;60932;60933	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
Novex-1	20361	61306;61307;61308	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
Novex-2	20428	61507;61508;61509	chr2:178557361;178557360;178557359	chr2:179422088;179422087;179422086
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-101
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.7886
• 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/I	None	None	0.669	N	0.419	0.177	0.362160248664	gnomAD-4.0.0	1.36832E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79883E-06	0	0
T/K	rs780957474	0.092	0.801	N	0.379	0.256	0.3085936734	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
T/K	rs780957474	0.092	0.801	N	0.379	0.256	0.3085936734	gnomAD-4.0.0	6.8416E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15931E-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
T/A	0.0606	likely_benign	0.0621	benign	-0.254	Destabilizing	0.625	D	0.33	neutral	N	0.407484312	None	None	N
T/C	0.3454	ambiguous	0.4006	ambiguous	-0.355	Destabilizing	0.998	D	0.415	neutral	None	None	None	None	N
T/D	0.2678	likely_benign	0.2669	benign	0.301	Stabilizing	0.728	D	0.385	neutral	None	None	None	None	N
T/E	0.3086	likely_benign	0.3052	benign	0.242	Stabilizing	0.842	D	0.384	neutral	None	None	None	None	N
T/F	0.3034	likely_benign	0.322	benign	-0.782	Destabilizing	0.949	D	0.419	neutral	None	None	None	None	N
T/G	0.1129	likely_benign	0.1198	benign	-0.381	Destabilizing	0.728	D	0.379	neutral	None	None	None	None	N
T/H	0.2008	likely_benign	0.223	benign	-0.544	Destabilizing	0.974	D	0.409	neutral	None	None	None	None	N
T/I	0.2947	likely_benign	0.3154	benign	-0.041	Destabilizing	0.669	D	0.419	neutral	N	0.456662339	None	None	N
T/K	0.2416	likely_benign	0.2564	benign	-0.231	Destabilizing	0.801	D	0.379	neutral	N	0.36711777	None	None	N
T/L	0.1273	likely_benign	0.1356	benign	-0.041	Destabilizing	0.016	N	0.229	neutral	None	None	None	None	N
T/M	0.1086	likely_benign	0.1125	benign	-0.129	Destabilizing	0.949	D	0.412	neutral	None	None	None	None	N
T/N	0.0709	likely_benign	0.0712	benign	-0.114	Destabilizing	0.007	N	0.141	neutral	None	None	None	None	N
T/P	0.1091	likely_benign	0.1271	benign	-0.084	Destabilizing	0.989	D	0.427	neutral	N	0.370832866	None	None	N
T/Q	0.214	likely_benign	0.2265	benign	-0.263	Destabilizing	0.974	D	0.423	neutral	None	None	None	None	N
T/R	0.2326	likely_benign	0.2456	benign	0.02	Stabilizing	0.934	D	0.423	neutral	N	0.363482819	None	None	N
T/S	0.0695	likely_benign	0.0745	benign	-0.324	Destabilizing	0.454	N	0.363	neutral	N	0.371870229	None	None	N
T/V	0.1877	likely_benign	0.1988	benign	-0.084	Destabilizing	0.728	D	0.321	neutral	None	None	None	None	N
T/W	0.6487	likely_pathogenic	0.6781	pathogenic	-0.841	Destabilizing	0.998	D	0.494	neutral	None	None	None	None	N
T/Y	0.2924	likely_benign	0.3098	benign	-0.514	Destabilizing	0.991	D	0.412	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.