TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21941	66046;66047;66048	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
N2AB	20300	61123;61124;61125	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
N2A	19373	58342;58343;58344	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
N2B	12876	38851;38852;38853	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
Novex-1	13001	39226;39227;39228	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
Novex-2	13068	39427;39428;39429	chr2:178582982;178582981;178582980	chr2:179447709;179447708;179447707
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-125
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.6903
• 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	None	N	0.109	0.122	0.332386209738	gnomAD-4.0.0	7.13798E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.26911E-07	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	0.0544	likely_benign	0.0602	benign	-0.258	Destabilizing	None	N	0.087	neutral	N	0.416832593	None	None	I
S/C	0.1318	likely_benign	0.1211	benign	-0.389	Destabilizing	0.356	N	0.273	neutral	None	None	None	None	I
S/D	0.3272	likely_benign	0.3307	benign	-0.127	Destabilizing	0.072	N	0.162	neutral	None	None	None	None	I
S/E	0.3759	ambiguous	0.3748	ambiguous	-0.239	Destabilizing	0.031	N	0.153	neutral	None	None	None	None	I
S/F	0.1995	likely_benign	0.2126	benign	-1.037	Destabilizing	0.12	N	0.345	neutral	None	None	None	None	I
S/G	0.0927	likely_benign	0.097	benign	-0.266	Destabilizing	0.016	N	0.19	neutral	None	None	None	None	I
S/H	0.3057	likely_benign	0.2843	benign	-0.619	Destabilizing	0.628	D	0.275	neutral	None	None	None	None	I
S/I	0.1053	likely_benign	0.1108	benign	-0.358	Destabilizing	0.001	N	0.135	neutral	None	None	None	None	I
S/K	0.4897	ambiguous	0.4635	ambiguous	-0.398	Destabilizing	0.031	N	0.155	neutral	None	None	None	None	I
S/L	0.0835	likely_benign	0.0885	benign	-0.358	Destabilizing	None	N	0.109	neutral	N	0.492042428	None	None	I
S/M	0.1678	likely_benign	0.1803	benign	-0.217	Destabilizing	0.214	N	0.26	neutral	None	None	None	None	I
S/N	0.1273	likely_benign	0.127	benign	-0.172	Destabilizing	0.136	N	0.181	neutral	None	None	None	None	I
S/P	0.0967	likely_benign	0.0934	benign	-0.305	Destabilizing	None	N	0.104	neutral	N	0.456044342	None	None	I
S/Q	0.3499	ambiguous	0.3395	benign	-0.397	Destabilizing	0.136	N	0.186	neutral	None	None	None	None	I
S/R	0.4259	ambiguous	0.4062	ambiguous	-0.191	Destabilizing	0.072	N	0.289	neutral	None	None	None	None	I
S/T	0.0786	likely_benign	0.0796	benign	-0.289	Destabilizing	0.012	N	0.185	neutral	N	0.47553418	None	None	I
S/V	0.1148	likely_benign	0.1235	benign	-0.305	Destabilizing	0.007	N	0.291	neutral	None	None	None	None	I
S/W	0.3988	ambiguous	0.3863	ambiguous	-1.121	Destabilizing	0.864	D	0.281	neutral	None	None	None	None	I
S/Y	0.2153	likely_benign	0.2184	benign	-0.818	Destabilizing	0.356	N	0.333	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.