TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26923	80992;80993;80994	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
N2AB	25282	76069;76070;76071	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
N2A	24355	73288;73289;73290	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
N2B	17858	53797;53798;53799	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
Novex-1	17983	54172;54173;54174	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
Novex-2	18050	54373;54374;54375	chr2:178565365;178565364;178565363	chr2:179430092;179430091;179430090
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: Ig-139
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.3684
• 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	0.988	N	0.652	0.428	0.402326594622	gnomAD-4.0.0	1.36857E-06	None	None	None	None	N	None	0	0	None	0	2.51991E-05	None	0	0	8.99549E-07	0	0
T/K	rs2154164717	None	0.988	N	0.625	0.427	0.355865052028	gnomAD-4.0.0	6.84284E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15955E-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	0.6798	likely_pathogenic	0.6105	pathogenic	-0.35	Destabilizing	0.067	N	0.284	neutral	N	0.460274017	None	None	N
T/C	0.9584	likely_pathogenic	0.9467	pathogenic	-0.182	Destabilizing	0.999	D	0.658	neutral	None	None	None	None	N
T/D	0.8094	likely_pathogenic	0.7588	pathogenic	-0.011	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	N
T/E	0.9242	likely_pathogenic	0.8974	pathogenic	-0.095	Destabilizing	0.991	D	0.633	neutral	None	None	None	None	N
T/F	0.9411	likely_pathogenic	0.9276	pathogenic	-0.847	Destabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	N
T/G	0.6736	likely_pathogenic	0.6385	pathogenic	-0.477	Destabilizing	0.938	D	0.567	neutral	None	None	None	None	N
T/H	0.8487	likely_pathogenic	0.8209	pathogenic	-0.816	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
T/I	0.9503	likely_pathogenic	0.9312	pathogenic	-0.136	Destabilizing	0.988	D	0.652	neutral	N	0.477430447	None	None	N
T/K	0.8447	likely_pathogenic	0.8278	pathogenic	-0.415	Destabilizing	0.988	D	0.625	neutral	N	0.457298276	None	None	N
T/L	0.7047	likely_pathogenic	0.6603	pathogenic	-0.136	Destabilizing	0.938	D	0.508	neutral	None	None	None	None	N
T/M	0.458	ambiguous	0.3885	ambiguous	0.125	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
T/N	0.4352	ambiguous	0.379	ambiguous	-0.151	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	N
T/P	0.8958	likely_pathogenic	0.8768	pathogenic	-0.179	Destabilizing	0.994	D	0.644	neutral	N	0.458565723	None	None	N
T/Q	0.8583	likely_pathogenic	0.8303	pathogenic	-0.419	Destabilizing	0.995	D	0.665	neutral	None	None	None	None	N
T/R	0.8418	likely_pathogenic	0.8208	pathogenic	-0.115	Destabilizing	0.994	D	0.633	neutral	N	0.467528945	None	None	N
T/S	0.409	ambiguous	0.3555	ambiguous	-0.337	Destabilizing	0.919	D	0.421	neutral	N	0.444775185	None	None	N
T/V	0.8751	likely_pathogenic	0.8396	pathogenic	-0.179	Destabilizing	0.938	D	0.46	neutral	None	None	None	None	N
T/W	0.9798	likely_pathogenic	0.9751	pathogenic	-0.854	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
T/Y	0.9145	likely_pathogenic	0.9044	pathogenic	-0.578	Destabilizing	0.998	D	0.723	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.