TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19865	59818;59819;59820	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
N2AB	18224	54895;54896;54897	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
N2A	17297	52114;52115;52116	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
N2B	10800	32623;32624;32625	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
Novex-1	10925	32998;32999;33000	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
Novex-2	10992	33199;33200;33201	chr2:178592412;178592411;178592410	chr2:179457139;179457138;179457137
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-119
• Domain position: 76
• Structural Position: 165
• Q(SASA): 0.5822
• 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
S/L	None	None	0.124	N	0.607	0.343	0.391156786388	gnomAD-4.0.0	1.59307E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.02645E-05

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	0.0934	likely_benign	0.0864	benign	-0.305	Destabilizing	0.055	N	0.421	neutral	N	0.494860269	None	None	I
S/C	0.0838	likely_benign	0.0755	benign	-0.247	Destabilizing	0.909	D	0.593	neutral	None	None	None	None	I
S/D	0.5155	ambiguous	0.5316	ambiguous	0.034	Stabilizing	0.272	N	0.471	neutral	None	None	None	None	I
S/E	0.4012	ambiguous	0.4432	ambiguous	-0.073	Destabilizing	0.272	N	0.439	neutral	None	None	None	None	I
S/F	0.2088	likely_benign	0.1971	benign	-0.97	Destabilizing	0.726	D	0.673	neutral	None	None	None	None	I
S/G	0.1225	likely_benign	0.1342	benign	-0.388	Destabilizing	0.272	N	0.442	neutral	None	None	None	None	I
S/H	0.2675	likely_benign	0.2751	benign	-0.922	Destabilizing	0.968	D	0.565	neutral	None	None	None	None	I
S/I	0.15	likely_benign	0.1366	benign	-0.218	Destabilizing	0.396	N	0.66	neutral	None	None	None	None	I
S/K	0.3831	ambiguous	0.3922	ambiguous	-0.444	Destabilizing	0.005	N	0.225	neutral	None	None	None	None	I
S/L	0.107	likely_benign	0.104	benign	-0.218	Destabilizing	0.124	N	0.607	neutral	N	0.501243052	None	None	I
S/M	0.1561	likely_benign	0.1469	benign	0.046	Stabilizing	0.909	D	0.568	neutral	None	None	None	None	I
S/N	0.1354	likely_benign	0.1352	benign	-0.157	Destabilizing	0.272	N	0.513	neutral	None	None	None	None	I
S/P	0.7397	likely_pathogenic	0.8147	pathogenic	-0.22	Destabilizing	0.667	D	0.555	neutral	N	0.513017431	None	None	I
S/Q	0.3051	likely_benign	0.3191	benign	-0.436	Destabilizing	0.567	D	0.499	neutral	None	None	None	None	I
S/R	0.3388	likely_benign	0.3475	ambiguous	-0.226	Destabilizing	0.396	N	0.509	neutral	None	None	None	None	I
S/T	0.0685	likely_benign	0.0659	benign	-0.259	Destabilizing	0.001	N	0.209	neutral	N	0.520957039	None	None	I
S/V	0.1518	likely_benign	0.1403	benign	-0.22	Destabilizing	0.157	N	0.581	neutral	None	None	None	None	I
S/W	0.3644	ambiguous	0.3923	ambiguous	-0.993	Destabilizing	0.968	D	0.71	prob.delet.	None	None	None	None	I
S/Y	0.2102	likely_benign	0.2093	benign	-0.704	Destabilizing	0.726	D	0.671	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.