TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15344	46255;46256;46257	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
N2AB	13703	41332;41333;41334	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
N2A	12776	38551;38552;38553	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
N2B	6279	19060;19061;19062	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
Novex-1	6404	19435;19436;19437	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
Novex-2	6471	19636;19637;19638	chr2:178620491;178620490;178620489	chr2:179485218;179485217;179485216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-105
• Domain position: 43
• Structural Position: 73
• Q(SASA): 0.4836
• 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
D/G	None	None	0.454	N	0.333	0.138	0.134241683229	gnomAD-4.0.0	1.59412E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88331E-05	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
D/A	0.4376	ambiguous	0.4408	ambiguous	-0.307	Destabilizing	0.454	N	0.375	neutral	D	0.525033376	None	None	N
D/C	0.7374	likely_pathogenic	0.7531	pathogenic	-0.034	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
D/E	0.4282	ambiguous	0.4835	ambiguous	-0.297	Destabilizing	0.625	D	0.361	neutral	N	0.456232475	None	None	N
D/F	0.8286	likely_pathogenic	0.8136	pathogenic	-0.228	Destabilizing	0.991	D	0.466	neutral	None	None	None	None	N
D/G	0.2339	likely_benign	0.2292	benign	-0.508	Destabilizing	0.454	N	0.333	neutral	N	0.44285326	None	None	N
D/H	0.4719	ambiguous	0.4902	ambiguous	-0.093	Destabilizing	0.966	D	0.316	neutral	D	0.527540822	None	None	N
D/I	0.7513	likely_pathogenic	0.7664	pathogenic	0.176	Stabilizing	0.974	D	0.474	neutral	None	None	None	None	N
D/K	0.657	likely_pathogenic	0.6685	pathogenic	0.209	Stabilizing	0.842	D	0.295	neutral	None	None	None	None	N
D/L	0.6468	likely_pathogenic	0.6455	pathogenic	0.176	Stabilizing	0.974	D	0.435	neutral	None	None	None	None	N
D/M	0.864	likely_pathogenic	0.8734	pathogenic	0.29	Stabilizing	0.998	D	0.45	neutral	None	None	None	None	N
D/N	0.1418	likely_benign	0.1471	benign	-0.078	Destabilizing	0.005	N	0.169	neutral	N	0.443154174	None	None	N
D/P	0.8654	likely_pathogenic	0.8778	pathogenic	0.037	Stabilizing	0.974	D	0.316	neutral	None	None	None	None	N
D/Q	0.6127	likely_pathogenic	0.6467	pathogenic	-0.033	Destabilizing	0.974	D	0.321	neutral	None	None	None	None	N
D/R	0.6669	likely_pathogenic	0.6835	pathogenic	0.38	Stabilizing	0.949	D	0.411	neutral	None	None	None	None	N
D/S	0.1743	likely_benign	0.1759	benign	-0.19	Destabilizing	0.08	N	0.175	neutral	None	None	None	None	N
D/T	0.3712	ambiguous	0.3776	ambiguous	-0.033	Destabilizing	0.728	D	0.325	neutral	None	None	None	None	N
D/V	0.5625	ambiguous	0.5817	pathogenic	0.037	Stabilizing	0.966	D	0.449	neutral	N	0.488358509	None	None	N
D/W	0.953	likely_pathogenic	0.9514	pathogenic	-0.099	Destabilizing	0.998	D	0.597	neutral	None	None	None	None	N
D/Y	0.5035	ambiguous	0.5107	ambiguous	None	Stabilizing	0.989	D	0.464	neutral	D	0.529045571	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.