TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29600	89023;89024;89025	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
N2AB	27959	84100;84101;84102	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
N2A	27032	81319;81320;81321	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
N2B	20535	61828;61829;61830	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
Novex-1	20660	62203;62204;62205	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
Novex-2	20727	62404;62405;62406	chr2:178554549;178554548;178554547	chr2:179419276;179419275;179419274
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-103
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.6488
• 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
K/I	rs548209283	0.527	0.999	N	0.653	0.368	0.561867705733	gnomAD-2.1.1	2.41E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.96066E-04	None	0	0	0
K/I	rs548209283	0.527	0.999	N	0.653	0.368	0.561867705733	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	4.1425E-04	0
K/I	rs548209283	0.527	0.999	N	0.653	0.368	0.561867705733	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	1E-03	None
K/I	rs548209283	0.527	0.999	N	0.653	0.368	0.561867705733	gnomAD-4.0.0	1.15267E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	2.25225E-04	0	1.0721E-04	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
K/A	0.3812	ambiguous	0.3826	ambiguous	-0.022	Destabilizing	0.992	D	0.527	neutral	None	None	None	None	N
K/C	0.7382	likely_pathogenic	0.7536	pathogenic	-0.217	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/D	0.7795	likely_pathogenic	0.764	pathogenic	0.042	Stabilizing	0.998	D	0.523	neutral	None	None	None	None	N
K/E	0.2406	likely_benign	0.2424	benign	0.053	Stabilizing	0.978	D	0.532	neutral	N	0.353553827	None	None	N
K/F	0.9047	likely_pathogenic	0.9154	pathogenic	-0.176	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
K/G	0.6056	likely_pathogenic	0.6141	pathogenic	-0.236	Destabilizing	0.999	D	0.508	neutral	None	None	None	None	N
K/H	0.4126	ambiguous	0.4168	ambiguous	-0.489	Destabilizing	1.0	D	0.509	neutral	None	None	None	None	N
K/I	0.5651	likely_pathogenic	0.5715	pathogenic	0.467	Stabilizing	0.999	D	0.653	neutral	N	0.43940473	None	None	N
K/L	0.5419	ambiguous	0.5525	ambiguous	0.467	Stabilizing	0.998	D	0.508	neutral	None	None	None	None	N
K/M	0.3994	ambiguous	0.3986	ambiguous	0.26	Stabilizing	1.0	D	0.509	neutral	None	None	None	None	N
K/N	0.6414	likely_pathogenic	0.6366	pathogenic	0.189	Stabilizing	0.998	D	0.58	neutral	N	0.424608635	None	None	N
K/P	0.5194	ambiguous	0.5079	ambiguous	0.333	Stabilizing	1.0	D	0.535	neutral	None	None	None	None	N
K/Q	0.1482	likely_benign	0.1564	benign	0.004	Stabilizing	0.775	D	0.225	neutral	N	0.359693152	None	None	N
K/R	0.0827	likely_benign	0.0865	benign	-0.057	Destabilizing	0.989	D	0.556	neutral	N	0.420472252	None	None	N
K/S	0.5387	ambiguous	0.5376	ambiguous	-0.316	Destabilizing	0.992	D	0.569	neutral	None	None	None	None	N
K/T	0.2643	likely_benign	0.2586	benign	-0.152	Destabilizing	0.998	D	0.529	neutral	N	0.429918455	None	None	N
K/V	0.4874	ambiguous	0.495	ambiguous	0.333	Stabilizing	0.999	D	0.546	neutral	None	None	None	None	N
K/W	0.8649	likely_pathogenic	0.883	pathogenic	-0.167	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/Y	0.8005	likely_pathogenic	0.8034	pathogenic	0.176	Stabilizing	1.0	D	0.593	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.