TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6074	18445;18446;18447	chr2:178730180;178730179;178730178	chr2:179594907;179594906;179594905
N2AB	5757	17494;17495;17496	chr2:178730180;178730179;178730178	chr2:179594907;179594906;179594905
N2A	4830	14713;14714;14715	chr2:178730180;178730179;178730178	chr2:179594907;179594906;179594905
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-44
• Domain position: 63
• Structural Position: 144
• Q(SASA): 0.1207
• 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
A/T	None	None	0.031	N	0.397	0.171	0.326881540566	gnomAD-4.0.0	1.36873E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7991E-06	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
A/C	0.5737	likely_pathogenic	0.5728	pathogenic	-1.748	Destabilizing	0.973	D	0.613	neutral	None	None	None	None	N
A/D	0.9229	likely_pathogenic	0.9331	pathogenic	-2.709	Highly Destabilizing	0.879	D	0.693	prob.neutral	N	0.508528115	None	None	N
A/E	0.8661	likely_pathogenic	0.8841	pathogenic	-2.625	Highly Destabilizing	0.906	D	0.667	neutral	None	None	None	None	N
A/F	0.8134	likely_pathogenic	0.8191	pathogenic	-1.13	Destabilizing	0.826	D	0.677	prob.neutral	None	None	None	None	N
A/G	0.2806	likely_benign	0.2896	benign	-1.641	Destabilizing	0.674	D	0.563	neutral	N	0.515022575	None	None	N
A/H	0.9501	likely_pathogenic	0.9528	pathogenic	-1.758	Destabilizing	0.991	D	0.663	neutral	None	None	None	None	N
A/I	0.3462	ambiguous	0.3319	benign	-0.4	Destabilizing	0.189	N	0.585	neutral	None	None	None	None	N
A/K	0.9451	likely_pathogenic	0.9514	pathogenic	-1.535	Destabilizing	0.906	D	0.665	neutral	None	None	None	None	N
A/L	0.3192	likely_benign	0.3099	benign	-0.4	Destabilizing	0.004	N	0.441	neutral	None	None	None	None	N
A/M	0.4344	ambiguous	0.4416	ambiguous	-0.606	Destabilizing	0.826	D	0.659	neutral	None	None	None	None	N
A/N	0.7832	likely_pathogenic	0.8085	pathogenic	-1.698	Destabilizing	0.906	D	0.683	prob.neutral	None	None	None	None	N
A/P	0.4711	ambiguous	0.4852	ambiguous	-0.656	Destabilizing	0.957	D	0.685	prob.neutral	N	0.503919759	None	None	N
A/Q	0.8649	likely_pathogenic	0.8716	pathogenic	-1.743	Destabilizing	0.967	D	0.659	neutral	None	None	None	None	N
A/R	0.9053	likely_pathogenic	0.9119	pathogenic	-1.301	Destabilizing	0.906	D	0.683	prob.neutral	None	None	None	None	N
A/S	0.1598	likely_benign	0.163	benign	-2.047	Highly Destabilizing	0.338	N	0.531	neutral	N	0.493689089	None	None	N
A/T	0.0932	likely_benign	0.1035	benign	-1.862	Destabilizing	0.031	N	0.397	neutral	N	0.510590903	None	None	N
A/V	0.124	likely_benign	0.1121	benign	-0.656	Destabilizing	0.003	N	0.404	neutral	N	0.407399459	None	None	N
A/W	0.9732	likely_pathogenic	0.9745	pathogenic	-1.66	Destabilizing	0.991	D	0.697	prob.neutral	None	None	None	None	N
A/Y	0.9344	likely_pathogenic	0.9373	pathogenic	-1.22	Destabilizing	0.906	D	0.679	prob.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.