TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9288	28087;28088;28089	chr2:178711968;178711967;178711966	chr2:179576695;179576694;179576693
N2AB	8971	27136;27137;27138	chr2:178711968;178711967;178711966	chr2:179576695;179576694;179576693
N2A	8044	24355;24356;24357	chr2:178711968;178711967;178711966	chr2:179576695;179576694;179576693
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: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-78
• Domain position: 84
• Structural Position: 169
• Q(SASA): 0.114
• 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/P	None	None	0.055	N	0.709	0.244	0.236890367714	gnomAD-4.0.0	1.61923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.06673E-05

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	0.2424	likely_benign	0.2804	benign	-0.588	Destabilizing	None	N	0.313	neutral	None	None	None	None	N
A/D	0.2801	likely_benign	0.3262	benign	-0.353	Destabilizing	0.038	N	0.681	prob.neutral	None	None	None	None	N
A/E	0.3041	likely_benign	0.3336	benign	-0.341	Destabilizing	0.029	N	0.672	neutral	N	0.521189112	None	None	N
A/F	0.241	likely_benign	0.3172	benign	-0.596	Destabilizing	0.356	N	0.725	prob.delet.	None	None	None	None	N
A/G	0.1281	likely_benign	0.1474	benign	-0.891	Destabilizing	0.012	N	0.443	neutral	N	0.50102727	None	None	N
A/H	0.42	ambiguous	0.4874	ambiguous	-0.973	Destabilizing	0.356	N	0.701	prob.neutral	None	None	None	None	N
A/I	0.1916	likely_benign	0.241	benign	0.068	Stabilizing	0.072	N	0.699	prob.neutral	None	None	None	None	N
A/K	0.4851	ambiguous	0.5623	ambiguous	-0.713	Destabilizing	0.038	N	0.669	neutral	None	None	None	None	N
A/L	0.1568	likely_benign	0.201	benign	0.068	Stabilizing	0.016	N	0.659	neutral	None	None	None	None	N
A/M	0.2044	likely_benign	0.2373	benign	-0.058	Destabilizing	0.628	D	0.705	prob.neutral	None	None	None	None	N
A/N	0.2171	likely_benign	0.2565	benign	-0.5	Destabilizing	0.038	N	0.688	prob.neutral	None	None	None	None	N
A/P	0.7669	likely_pathogenic	0.8949	pathogenic	-0.109	Destabilizing	0.055	N	0.709	prob.delet.	N	0.507639061	None	None	N
A/Q	0.3826	ambiguous	0.4184	ambiguous	-0.543	Destabilizing	0.072	N	0.731	prob.delet.	None	None	None	None	N
A/R	0.4413	ambiguous	0.5208	ambiguous	-0.548	Destabilizing	0.072	N	0.711	prob.delet.	None	None	None	None	N
A/S	0.0669	likely_benign	0.0736	benign	-0.958	Destabilizing	None	N	0.166	neutral	N	0.400900349	None	None	N
A/T	0.0684	likely_benign	0.0699	benign	-0.825	Destabilizing	0.012	N	0.521	neutral	N	0.435359639	None	None	N
A/V	0.1124	likely_benign	0.1318	benign	-0.109	Destabilizing	0.024	N	0.561	neutral	N	0.494061226	None	None	N
A/W	0.6174	likely_pathogenic	0.728	pathogenic	-0.982	Destabilizing	0.864	D	0.72	prob.delet.	None	None	None	None	N
A/Y	0.3224	likely_benign	0.4228	ambiguous	-0.505	Destabilizing	0.356	N	0.727	prob.delet.	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.