TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31231	93916;93917;93918	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
N2AB	29590	88993;88994;88995	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
N2A	28663	86212;86213;86214	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
N2B	22166	66721;66722;66723	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
Novex-1	22291	67096;67097;67098	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
Novex-2	22358	67297;67298;67299	chr2:178547935;178547934;178547933	chr2:179412662;179412661;179412660
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-151
• Domain position: 14
• Structural Position: 25
• Q(SASA): 0.2343
• 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	rs1060500565	None	0.001	N	0.184	0.068	0.0482279557977	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
S/A	0.0948	likely_benign	0.0993	benign	-0.515	Destabilizing	0.004	N	0.191	neutral	None	None	None	None	N
S/C	0.1119	likely_benign	0.1055	benign	-0.256	Destabilizing	0.928	D	0.369	neutral	N	0.511891185	None	None	N
S/D	0.3389	likely_benign	0.3077	benign	-0.2	Destabilizing	0.241	N	0.381	neutral	None	None	None	None	N
S/E	0.4297	ambiguous	0.4131	ambiguous	-0.286	Destabilizing	0.388	N	0.391	neutral	None	None	None	None	N
S/F	0.1835	likely_benign	0.1855	benign	-1.099	Destabilizing	0.818	D	0.446	neutral	None	None	None	None	N
S/G	0.1002	likely_benign	0.0926	benign	-0.64	Destabilizing	0.09	N	0.388	neutral	N	0.466713469	None	None	N
S/H	0.2686	likely_benign	0.2467	benign	-1.235	Destabilizing	0.818	D	0.367	neutral	None	None	None	None	N
S/I	0.1397	likely_benign	0.1368	benign	-0.307	Destabilizing	0.457	N	0.401	neutral	N	0.501116831	None	None	N
S/K	0.5346	ambiguous	0.482	ambiguous	-0.535	Destabilizing	0.388	N	0.384	neutral	None	None	None	None	N
S/L	0.0854	likely_benign	0.0877	benign	-0.307	Destabilizing	0.241	N	0.389	neutral	None	None	None	None	N
S/M	0.1447	likely_benign	0.1461	benign	0.183	Stabilizing	0.818	D	0.367	neutral	None	None	None	None	N
S/N	0.1016	likely_benign	0.0949	benign	-0.296	Destabilizing	0.001	N	0.184	neutral	N	0.41901831	None	None	N
S/P	0.841	likely_pathogenic	0.8419	pathogenic	-0.348	Destabilizing	0.818	D	0.334	neutral	None	None	None	None	N
S/Q	0.3724	ambiguous	0.346	ambiguous	-0.624	Destabilizing	0.818	D	0.395	neutral	None	None	None	None	N
S/R	0.5274	ambiguous	0.4822	ambiguous	-0.29	Destabilizing	0.627	D	0.337	neutral	N	0.48149092	None	None	N
S/T	0.0772	likely_benign	0.0799	benign	-0.387	Destabilizing	0.001	N	0.218	neutral	N	0.437950787	None	None	N
S/V	0.1446	likely_benign	0.1454	benign	-0.348	Destabilizing	0.241	N	0.375	neutral	None	None	None	None	N
S/W	0.3768	ambiguous	0.3639	ambiguous	-1.066	Destabilizing	0.981	D	0.56	neutral	None	None	None	None	N
S/Y	0.1665	likely_benign	0.1555	benign	-0.799	Destabilizing	0.818	D	0.446	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.