TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30205	90838;90839;90840	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
N2AB	28564	85915;85916;85917	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
N2A	27637	83134;83135;83136	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
N2B	21140	63643;63644;63645	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
Novex-1	21265	64018;64019;64020	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
Novex-2	21332	64219;64220;64221	chr2:178552287;178552286;178552285	chr2:179417014;179417013;179417012
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-148
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.2122
• 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
I/N	rs1283032526	-1.9	0.998	D	0.811	0.521	0.838418281918	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
I/N	rs1283032526	-1.9	0.998	D	0.811	0.521	0.838418281918	gnomAD-4.0.0	3.18458E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.7187E-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
I/A	0.6384	likely_pathogenic	0.4648	ambiguous	-2.35	Highly Destabilizing	0.931	D	0.661	neutral	None	None	None	None	N
I/C	0.7884	likely_pathogenic	0.6742	pathogenic	-1.599	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
I/D	0.9444	likely_pathogenic	0.8762	pathogenic	-2.729	Highly Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
I/E	0.843	likely_pathogenic	0.72	pathogenic	-2.545	Highly Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
I/F	0.2695	likely_benign	0.1861	benign	-1.382	Destabilizing	0.994	D	0.596	neutral	N	0.510105327	None	None	N
I/G	0.9076	likely_pathogenic	0.8091	pathogenic	-2.829	Highly Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
I/H	0.7328	likely_pathogenic	0.572	pathogenic	-2.33	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
I/K	0.7406	likely_pathogenic	0.5732	pathogenic	-1.705	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
I/L	0.165	likely_benign	0.1296	benign	-0.983	Destabilizing	0.689	D	0.378	neutral	N	0.472240372	None	None	N
I/M	0.1651	likely_benign	0.1255	benign	-1.001	Destabilizing	0.994	D	0.614	neutral	N	0.495559949	None	None	N
I/N	0.5542	ambiguous	0.3729	ambiguous	-1.945	Destabilizing	0.998	D	0.811	deleterious	D	0.524322631	None	None	N
I/P	0.9872	likely_pathogenic	0.9777	pathogenic	-1.419	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
I/Q	0.6912	likely_pathogenic	0.5432	ambiguous	-1.872	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
I/R	0.657	likely_pathogenic	0.4935	ambiguous	-1.39	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
I/S	0.5385	ambiguous	0.3629	ambiguous	-2.56	Highly Destabilizing	0.994	D	0.765	deleterious	N	0.471720297	None	None	N
I/T	0.3563	ambiguous	0.2074	benign	-2.252	Highly Destabilizing	0.961	D	0.663	neutral	N	0.411690558	None	None	N
I/V	0.1145	likely_benign	0.0875	benign	-1.419	Destabilizing	0.122	N	0.247	neutral	N	0.419501965	None	None	N
I/W	0.9112	likely_pathogenic	0.8469	pathogenic	-1.782	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
I/Y	0.6816	likely_pathogenic	0.5256	ambiguous	-1.493	Destabilizing	0.999	D	0.715	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.