TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5248	15967;15968;15969	chr2:178733647;178733646;178733645	chr2:179598374;179598373;179598372
N2AB	4931	15016;15017;15018	chr2:178733647;178733646;178733645	chr2:179598374;179598373;179598372
N2A	4004	12235;12236;12237	chr2:178733647;178733646;178733645	chr2:179598374;179598373;179598372
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-35
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.4495
• 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	rs2080939542	None	0.959	N	0.288	0.193	0.247872288689	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs2080939542	None	0.959	N	0.288	0.193	0.247872288689	gnomAD-4.0.0	6.57056E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.4699E-05	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	0.0877	likely_benign	0.0917	benign	-0.359	Destabilizing	0.863	D	0.288	neutral	None	None	None	None	N
S/C	0.1186	likely_benign	0.1144	benign	-0.334	Destabilizing	0.999	D	0.468	neutral	D	0.614950487	None	None	N
S/D	0.5024	ambiguous	0.5073	ambiguous	-0.034	Destabilizing	0.939	D	0.28	neutral	None	None	None	None	N
S/E	0.461	ambiguous	0.4865	ambiguous	-0.118	Destabilizing	0.759	D	0.279	neutral	None	None	None	None	N
S/F	0.1461	likely_benign	0.1455	benign	-0.811	Destabilizing	0.991	D	0.57	neutral	None	None	None	None	N
S/G	0.1233	likely_benign	0.1187	benign	-0.501	Destabilizing	0.906	D	0.256	neutral	D	0.613277725	None	None	N
S/H	0.296	likely_benign	0.2841	benign	-0.964	Destabilizing	0.991	D	0.472	neutral	None	None	None	None	N
S/I	0.1315	likely_benign	0.124	benign	-0.113	Destabilizing	0.134	N	0.408	neutral	N	0.511614229	None	None	N
S/K	0.4387	ambiguous	0.4454	ambiguous	-0.629	Destabilizing	0.17	N	0.125	neutral	None	None	None	None	N
S/L	0.0925	likely_benign	0.0947	benign	-0.113	Destabilizing	0.759	D	0.527	neutral	None	None	None	None	N
S/M	0.1607	likely_benign	0.1621	benign	0.078	Stabilizing	0.991	D	0.473	neutral	None	None	None	None	N
S/N	0.138	likely_benign	0.129	benign	-0.327	Destabilizing	0.959	D	0.288	neutral	N	0.514095914	None	None	N
S/P	0.6951	likely_pathogenic	0.7167	pathogenic	-0.165	Destabilizing	0.997	D	0.435	neutral	None	None	None	None	N
S/Q	0.3446	ambiguous	0.3567	ambiguous	-0.588	Destabilizing	0.2	N	0.123	neutral	None	None	None	None	N
S/R	0.3657	ambiguous	0.3644	ambiguous	-0.371	Destabilizing	0.852	D	0.387	neutral	N	0.50832044	None	None	N
S/T	0.0805	likely_benign	0.0819	benign	-0.421	Destabilizing	0.906	D	0.261	neutral	N	0.492150445	None	None	N
S/V	0.1455	likely_benign	0.1505	benign	-0.165	Destabilizing	0.759	D	0.51	neutral	None	None	None	None	N
S/W	0.3345	likely_benign	0.3364	benign	-0.809	Destabilizing	0.999	D	0.585	neutral	None	None	None	None	N
S/Y	0.1499	likely_benign	0.1486	benign	-0.549	Destabilizing	0.997	D	0.57	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.