TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5117	15574;15575;15576	chr2:178734475;178734474;178734473	chr2:179599202;179599201;179599200
N2AB	4800	14623;14624;14625	chr2:178734475;178734474;178734473	chr2:179599202;179599201;179599200
N2A	3873	11842;11843;11844	chr2:178734475;178734474;178734473	chr2:179599202;179599201;179599200
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-34
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.4654
• 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
S/N	None	None	0.99	D	0.46	0.283	0.327952845175	gnomAD-4.0.0	3.18324E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88303E-05	0	2.85892E-06	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
S/A	0.086	likely_benign	0.1053	benign	-0.211	Destabilizing	0.469	N	0.171	neutral	None	None	None	None	N
S/C	0.2006	likely_benign	0.2747	benign	-0.371	Destabilizing	1.0	D	0.581	neutral	D	0.74636799	None	None	N
S/D	0.6704	likely_pathogenic	0.6959	pathogenic	0.453	Stabilizing	0.993	D	0.427	neutral	None	None	None	None	N
S/E	0.7539	likely_pathogenic	0.7792	pathogenic	0.363	Stabilizing	0.993	D	0.425	neutral	None	None	None	None	N
S/F	0.3156	likely_benign	0.3896	ambiguous	-0.898	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
S/G	0.0969	likely_benign	0.118	benign	-0.29	Destabilizing	0.135	N	0.149	neutral	N	0.51436123	None	None	N
S/H	0.5313	ambiguous	0.5879	pathogenic	-0.683	Destabilizing	1.0	D	0.571	neutral	None	None	None	None	N
S/I	0.2543	likely_benign	0.3272	benign	-0.137	Destabilizing	0.997	D	0.608	neutral	D	0.586154736	None	None	N
S/K	0.8591	likely_pathogenic	0.8845	pathogenic	-0.271	Destabilizing	0.993	D	0.423	neutral	None	None	None	None	N
S/L	0.1311	likely_benign	0.1678	benign	-0.137	Destabilizing	0.985	D	0.483	neutral	None	None	None	None	N
S/M	0.2694	likely_benign	0.3352	benign	-0.154	Destabilizing	1.0	D	0.574	neutral	None	None	None	None	N
S/N	0.1752	likely_benign	0.2106	benign	-0.116	Destabilizing	0.99	D	0.46	neutral	D	0.546018	None	None	N
S/P	0.0997	likely_benign	0.1216	benign	-0.135	Destabilizing	0.998	D	0.538	neutral	None	None	None	None	N
S/Q	0.6388	likely_pathogenic	0.7027	pathogenic	-0.278	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
S/R	0.8079	likely_pathogenic	0.8359	pathogenic	-0.126	Destabilizing	0.997	D	0.543	neutral	D	0.580255734	None	None	N
S/T	0.103	likely_benign	0.1267	benign	-0.218	Destabilizing	0.98	D	0.442	neutral	N	0.507688082	None	None	N
S/V	0.2366	likely_benign	0.3057	benign	-0.135	Destabilizing	0.996	D	0.513	neutral	None	None	None	None	N
S/W	0.5074	ambiguous	0.5696	pathogenic	-0.967	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
S/Y	0.2928	likely_benign	0.3326	benign	-0.638	Destabilizing	0.999	D	0.615	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.