TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30750	92473;92474;92475	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
N2AB	29109	87550;87551;87552	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
N2A	28182	84769;84770;84771	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
N2B	21685	65278;65279;65280	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
Novex-1	21810	65653;65654;65655	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
Novex-2	21877	65854;65855;65856	chr2:178549378;178549377;178549376	chr2:179414105;179414104;179414103
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-112
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.7531
• 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
E/G	None	None	0.993	N	0.601	0.408	0.4018988957	gnomAD-4.0.0	6.84205E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99457E-07	0	0
E/V	None	None	0.997	N	0.687	0.455	0.488757021912	gnomAD-4.0.0	6.84205E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15937E-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
E/A	0.1446	likely_benign	0.1465	benign	-0.295	Destabilizing	0.977	D	0.603	neutral	N	0.497183597	None	None	I
E/C	0.8057	likely_pathogenic	0.807	pathogenic	0.076	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/D	0.087	likely_benign	0.0842	benign	-0.243	Destabilizing	0.117	N	0.213	neutral	N	0.480501991	None	None	I
E/F	0.7535	likely_pathogenic	0.758	pathogenic	-0.282	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
E/G	0.1829	likely_benign	0.1819	benign	-0.475	Destabilizing	0.993	D	0.601	neutral	N	0.480424593	None	None	I
E/H	0.4294	ambiguous	0.4423	ambiguous	-0.062	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/I	0.3527	ambiguous	0.3504	ambiguous	0.137	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	I
E/K	0.1509	likely_benign	0.1488	benign	0.388	Stabilizing	0.977	D	0.584	neutral	N	0.463801742	None	None	I
E/L	0.4125	ambiguous	0.4108	ambiguous	0.137	Stabilizing	0.998	D	0.665	neutral	None	None	None	None	I
E/M	0.4746	ambiguous	0.4723	ambiguous	0.253	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
E/N	0.2018	likely_benign	0.2066	benign	0.171	Stabilizing	0.99	D	0.704	prob.neutral	None	None	None	None	I
E/P	0.2844	likely_benign	0.2813	benign	0.013	Stabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	I
E/Q	0.149	likely_benign	0.1546	benign	0.191	Stabilizing	0.997	D	0.647	neutral	N	0.507053874	None	None	I
E/R	0.255	likely_benign	0.2509	benign	0.541	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	I
E/S	0.1818	likely_benign	0.1858	benign	-0.009	Destabilizing	0.983	D	0.608	neutral	None	None	None	None	I
E/T	0.2157	likely_benign	0.217	benign	0.136	Stabilizing	0.995	D	0.642	neutral	None	None	None	None	I
E/V	0.2143	likely_benign	0.2111	benign	0.013	Stabilizing	0.997	D	0.687	prob.neutral	N	0.488880836	None	None	I
E/W	0.9012	likely_pathogenic	0.9012	pathogenic	-0.174	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
E/Y	0.6039	likely_pathogenic	0.6142	pathogenic	-0.045	Destabilizing	1.0	D	0.673	neutral	None	None	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.