TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29401	88426;88427;88428	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
N2AB	27760	83503;83504;83505	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
N2A	26833	80722;80723;80724	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
N2B	20336	61231;61232;61233	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
Novex-1	20461	61606;61607;61608	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
Novex-2	20528	61807;61808;61809	chr2:178556953;178556952;178556951	chr2:179421680;179421679;179421678
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-102
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.4872
• 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
T/I	None	None	0.004	N	0.281	0.109	0.252162846088	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99441E-07	0	0
T/N	None	None	0.015	N	0.234	0.099	0.224531998449	gnomAD-4.0.0	6.84215E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99441E-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
T/A	0.0966	likely_benign	0.0939	benign	-0.784	Destabilizing	0.334	N	0.402	neutral	N	0.468330591	None	None	N
T/C	0.4388	ambiguous	0.4267	ambiguous	-0.344	Destabilizing	0.982	D	0.581	neutral	None	None	None	None	N
T/D	0.5023	ambiguous	0.4468	ambiguous	-0.041	Destabilizing	0.539	D	0.5	neutral	None	None	None	None	N
T/E	0.3675	ambiguous	0.3201	benign	-0.076	Destabilizing	0.7	D	0.497	neutral	None	None	None	None	N
T/F	0.309	likely_benign	0.2507	benign	-1.041	Destabilizing	0.7	D	0.639	neutral	None	None	None	None	N
T/G	0.2873	likely_benign	0.2721	benign	-0.994	Destabilizing	0.399	N	0.505	neutral	None	None	None	None	N
T/H	0.2751	likely_benign	0.2508	benign	-1.257	Destabilizing	0.947	D	0.632	neutral	None	None	None	None	N
T/I	0.1524	likely_benign	0.123	benign	-0.329	Destabilizing	0.004	N	0.281	neutral	N	0.468650201	None	None	N
T/K	0.2335	likely_benign	0.198	benign	-0.629	Destabilizing	0.7	D	0.515	neutral	None	None	None	None	N
T/L	0.0953	likely_benign	0.0849	benign	-0.329	Destabilizing	0.103	N	0.41	neutral	None	None	None	None	N
T/M	0.0908	likely_benign	0.087	benign	0.034	Stabilizing	0.898	D	0.579	neutral	None	None	None	None	N
T/N	0.123	likely_benign	0.116	benign	-0.449	Destabilizing	0.015	N	0.234	neutral	N	0.494970011	None	None	N
T/P	0.1504	likely_benign	0.1504	benign	-0.45	Destabilizing	0.916	D	0.573	neutral	N	0.495032901	None	None	N
T/Q	0.2023	likely_benign	0.191	benign	-0.659	Destabilizing	0.826	D	0.571	neutral	None	None	None	None	N
T/R	0.2206	likely_benign	0.1848	benign	-0.33	Destabilizing	0.826	D	0.573	neutral	None	None	None	None	N
T/S	0.1102	likely_benign	0.1088	benign	-0.728	Destabilizing	0.334	N	0.416	neutral	N	0.467148691	None	None	N
T/V	0.1267	likely_benign	0.1133	benign	-0.45	Destabilizing	0.103	N	0.403	neutral	None	None	None	None	N
T/W	0.7227	likely_pathogenic	0.673	pathogenic	-0.972	Destabilizing	0.982	D	0.669	neutral	None	None	None	None	N
T/Y	0.3611	ambiguous	0.3259	benign	-0.745	Destabilizing	0.826	D	0.64	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.