TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29259	88000;88001;88002	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
N2AB	27618	83077;83078;83079	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
N2A	26691	80296;80297;80298	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
N2B	20194	60805;60806;60807	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
Novex-1	20319	61180;61181;61182	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
Novex-2	20386	61381;61382;61383	chr2:178557487;178557486;178557485	chr2:179422214;179422213;179422212
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-101
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.6189
• 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
H/Q	None	None	0.684	N	0.552	0.148	0.171388866994	gnomAD-4.0.0	6.84178E-07	None	None	None	None	I	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
H/A	0.5109	ambiguous	0.5587	ambiguous	0.091	Stabilizing	0.543	D	0.473	neutral	None	None	None	None	I
H/C	0.2886	likely_benign	0.3567	ambiguous	0.685	Stabilizing	0.996	D	0.539	neutral	None	None	None	None	I
H/D	0.4183	ambiguous	0.4628	ambiguous	-0.195	Destabilizing	0.521	D	0.526	neutral	N	0.431051818	None	None	I
H/E	0.4822	ambiguous	0.5269	ambiguous	-0.137	Destabilizing	0.543	D	0.521	neutral	None	None	None	None	I
H/F	0.4643	ambiguous	0.4616	ambiguous	1.027	Stabilizing	0.984	D	0.605	neutral	None	None	None	None	I
H/G	0.4822	ambiguous	0.5291	ambiguous	-0.236	Destabilizing	0.373	N	0.485	neutral	None	None	None	None	I
H/I	0.6246	likely_pathogenic	0.6436	pathogenic	0.954	Stabilizing	0.953	D	0.596	neutral	None	None	None	None	I
H/K	0.3815	ambiguous	0.3835	ambiguous	0.121	Stabilizing	0.016	N	0.222	neutral	None	None	None	None	I
H/L	0.2043	likely_benign	0.2484	benign	0.954	Stabilizing	0.815	D	0.541	neutral	N	0.467743337	None	None	I
H/M	0.5825	likely_pathogenic	0.6025	pathogenic	0.681	Stabilizing	0.984	D	0.557	neutral	None	None	None	None	I
H/N	0.1335	likely_benign	0.1427	benign	0.037	Stabilizing	0.003	N	0.142	neutral	N	0.409215109	None	None	I
H/P	0.4893	ambiguous	0.5543	ambiguous	0.691	Stabilizing	0.979	D	0.619	neutral	N	0.46843677	None	None	I
H/Q	0.2596	likely_benign	0.2927	benign	0.208	Stabilizing	0.684	D	0.552	neutral	N	0.408695034	None	None	I
H/R	0.1833	likely_benign	0.2065	benign	-0.55	Destabilizing	0.521	D	0.502	neutral	N	0.452120524	None	None	I
H/S	0.3818	ambiguous	0.4196	ambiguous	0.171	Stabilizing	0.373	N	0.479	neutral	None	None	None	None	I
H/T	0.4819	ambiguous	0.5188	ambiguous	0.335	Stabilizing	0.742	D	0.548	neutral	None	None	None	None	I
H/V	0.5209	ambiguous	0.5501	ambiguous	0.691	Stabilizing	0.854	D	0.586	neutral	None	None	None	None	I
H/W	0.5288	ambiguous	0.5798	pathogenic	1.12	Stabilizing	0.996	D	0.568	neutral	None	None	None	None	I
H/Y	0.1601	likely_benign	0.1761	benign	1.313	Stabilizing	0.931	D	0.525	neutral	N	0.461606799	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.