TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21906	65941;65942;65943	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
N2AB	20265	61018;61019;61020	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
N2A	19338	58237;58238;58239	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
N2B	12841	38746;38747;38748	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
Novex-1	12966	39121;39122;39123	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
Novex-2	13033	39322;39323;39324	chr2:178583087;178583086;178583085	chr2:179447814;179447813;179447812
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-125
• Domain position: 41
• Structural Position: 70
• Q(SASA): 0.3416
• 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
P/R	rs1193931137	None	0.188	N	0.387	0.178	0.395894371353	gnomAD-4.0.0	6.85319E-07	None	None	None	None	N	None	2.9924E-05	0	None	0	0	None	0	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
P/A	0.0712	likely_benign	0.0706	benign	-0.343	Destabilizing	None	N	0.122	neutral	N	0.445400487	None	None	N
P/C	0.5409	ambiguous	0.4539	ambiguous	-0.513	Destabilizing	0.824	D	0.397	neutral	None	None	None	None	N
P/D	0.3767	ambiguous	0.3326	benign	-0.54	Destabilizing	0.149	N	0.347	neutral	None	None	None	None	N
P/E	0.2188	likely_benign	0.1977	benign	-0.652	Destabilizing	0.081	N	0.319	neutral	None	None	None	None	N
P/F	0.4927	ambiguous	0.415	ambiguous	-0.664	Destabilizing	0.38	N	0.423	neutral	None	None	None	None	N
P/G	0.2715	likely_benign	0.2389	benign	-0.453	Destabilizing	0.081	N	0.338	neutral	None	None	None	None	N
P/H	0.2083	likely_benign	0.1637	benign	-0.111	Destabilizing	0.698	D	0.371	neutral	None	None	None	None	N
P/I	0.2643	likely_benign	0.2355	benign	-0.197	Destabilizing	0.081	N	0.416	neutral	None	None	None	None	N
P/K	0.2485	likely_benign	0.2113	benign	-0.434	Destabilizing	0.081	N	0.306	neutral	None	None	None	None	N
P/L	0.1034	likely_benign	0.0902	benign	-0.197	Destabilizing	None	N	0.217	neutral	N	0.461698091	None	None	N
P/M	0.2341	likely_benign	0.2109	benign	-0.395	Destabilizing	0.38	N	0.383	neutral	None	None	None	None	N
P/N	0.2546	likely_benign	0.224	benign	-0.131	Destabilizing	0.38	N	0.393	neutral	None	None	None	None	N
P/Q	0.1302	likely_benign	0.1068	benign	-0.373	Destabilizing	0.001	N	0.198	neutral	N	0.470008143	None	None	N
P/R	0.1913	likely_benign	0.1565	benign	0.05	Stabilizing	0.188	N	0.387	neutral	N	0.482188007	None	None	N
P/S	0.1216	likely_benign	0.1116	benign	-0.392	Destabilizing	0.062	N	0.331	neutral	N	0.424926428	None	None	N
P/T	0.0929	likely_benign	0.086	benign	-0.413	Destabilizing	0.117	N	0.324	neutral	N	0.458772429	None	None	N
P/V	0.1645	likely_benign	0.1532	benign	-0.214	Destabilizing	0.035	N	0.348	neutral	None	None	None	None	N
P/W	0.6461	likely_pathogenic	0.538	ambiguous	-0.773	Destabilizing	0.935	D	0.442	neutral	None	None	None	None	N
P/Y	0.408	ambiguous	0.345	ambiguous	-0.464	Destabilizing	0.555	D	0.419	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.