TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5389	16390;16391;16392	chr2:178733011;178733010;178733009	chr2:179597738;179597737;179597736
N2AB	5072	15439;15440;15441	chr2:178733011;178733010;178733009	chr2:179597738;179597737;179597736
N2A	4145	12658;12659;12660	chr2:178733011;178733010;178733009	chr2:179597738;179597737;179597736
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: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-37
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2333
• 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/F	rs780968460	-0.286	0.667	N	0.713	0.424	0.702110701905	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
S/F	rs780968460	-0.286	0.667	N	0.713	0.424	0.702110701905	gnomAD-4.0.0	3.18385E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85878E-06	1.43303E-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	0.0767	likely_benign	0.082	benign	-0.637	Destabilizing	None	N	0.329	neutral	D	0.52725108	None	None	N
S/C	0.1203	likely_benign	0.1162	benign	-0.312	Destabilizing	0.883	D	0.673	neutral	N	0.501931523	None	None	N
S/D	0.4358	ambiguous	0.4485	ambiguous	-0.212	Destabilizing	0.567	D	0.584	neutral	None	None	None	None	N
S/E	0.4829	ambiguous	0.4988	ambiguous	-0.116	Destabilizing	0.272	N	0.589	neutral	None	None	None	None	N
S/F	0.1555	likely_benign	0.1618	benign	-0.6	Destabilizing	0.667	D	0.713	prob.delet.	N	0.496246757	None	None	N
S/G	0.1212	likely_benign	0.1266	benign	-0.97	Destabilizing	0.072	N	0.579	neutral	None	None	None	None	N
S/H	0.3099	likely_benign	0.2996	benign	-1.213	Destabilizing	0.968	D	0.673	neutral	None	None	None	None	N
S/I	0.1674	likely_benign	0.1715	benign	0.167	Stabilizing	0.567	D	0.683	prob.neutral	None	None	None	None	N
S/K	0.6193	likely_pathogenic	0.6076	pathogenic	-0.284	Destabilizing	0.272	N	0.588	neutral	None	None	None	None	N
S/L	0.0967	likely_benign	0.0997	benign	0.167	Stabilizing	0.157	N	0.623	neutral	None	None	None	None	N
S/M	0.1903	likely_benign	0.2018	benign	0.15	Stabilizing	0.909	D	0.674	neutral	None	None	None	None	N
S/N	0.1736	likely_benign	0.1709	benign	-0.556	Destabilizing	0.726	D	0.587	neutral	None	None	None	None	N
S/P	0.9086	likely_pathogenic	0.9193	pathogenic	-0.066	Destabilizing	0.497	N	0.673	neutral	D	0.52792259	None	None	N
S/Q	0.4375	ambiguous	0.4341	ambiguous	-0.482	Destabilizing	0.726	D	0.606	neutral	None	None	None	None	N
S/R	0.4963	ambiguous	0.4788	ambiguous	-0.377	Destabilizing	0.567	D	0.679	prob.neutral	None	None	None	None	N
S/T	0.0819	likely_benign	0.0814	benign	-0.472	Destabilizing	0.124	N	0.571	neutral	N	0.448270221	None	None	N
S/V	0.1506	likely_benign	0.16	benign	-0.066	Destabilizing	0.157	N	0.635	neutral	None	None	None	None	N
S/W	0.3104	likely_benign	0.3102	benign	-0.7	Destabilizing	0.968	D	0.718	prob.delet.	None	None	None	None	N
S/Y	0.1656	likely_benign	0.1666	benign	-0.334	Destabilizing	0.667	D	0.719	prob.delet.	D	0.530427458	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.