TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2767	8524;8525;8526	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
N2AB	2767	8524;8525;8526	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
N2A	2767	8524;8525;8526	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
N2B	2721	8386;8387;8388	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
Novex-1	2721	8386;8387;8388	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
Novex-2	2721	8386;8387;8388	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218
Novex-3	2767	8524;8525;8526	chr2:178770493;178770492;178770491	chr2:179635220;179635219;179635218

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-17
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.3598
• 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/N	None	None	0.733	N	0.256	0.161	0.188950314367	gnomAD-4.0.0	1.59052E-06	None	None	None	None	N	None	0	0	None	0	2.77362E-05	None	0	0	0	0	0
K/R	None	None	0.217	N	0.281	0.225	0.247322355667	gnomAD-4.0.0	1.59051E-06	None	None	None	None	N	None	5.65163E-05	0	None	0	0	None	0	0	0	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
K/A	0.3441	ambiguous	0.3786	ambiguous	-0.523	Destabilizing	0.996	D	0.486	neutral	None	None	None	None	N
K/C	0.6822	likely_pathogenic	0.7197	pathogenic	-0.705	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/D	0.5575	ambiguous	0.6032	pathogenic	-0.645	Destabilizing	0.995	D	0.552	neutral	None	None	None	None	N
K/E	0.1521	likely_benign	0.1593	benign	-0.546	Destabilizing	0.989	D	0.461	neutral	D	0.537709462	None	None	N
K/F	0.7329	likely_pathogenic	0.7786	pathogenic	-0.374	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
K/G	0.4125	ambiguous	0.4523	ambiguous	-0.883	Destabilizing	0.992	D	0.571	neutral	None	None	None	None	N
K/H	0.2919	likely_benign	0.3044	benign	-1.362	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
K/I	0.3591	ambiguous	0.4101	ambiguous	0.405	Stabilizing	0.999	D	0.728	prob.delet.	D	0.598383171	None	None	N
K/L	0.3482	ambiguous	0.3869	ambiguous	0.405	Stabilizing	0.999	D	0.6	neutral	None	None	None	None	N
K/M	0.2529	likely_benign	0.2714	benign	0.407	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
K/N	0.3327	likely_benign	0.3745	ambiguous	-0.723	Destabilizing	0.733	D	0.256	neutral	N	0.508205632	None	None	N
K/P	0.7145	likely_pathogenic	0.7542	pathogenic	0.127	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
K/Q	0.1112	likely_benign	0.1119	benign	-0.844	Destabilizing	0.997	D	0.52	neutral	D	0.590564712	None	None	N
K/R	0.0794	likely_benign	0.0775	benign	-0.75	Destabilizing	0.217	N	0.281	neutral	N	0.502409139	None	None	N
K/S	0.3531	ambiguous	0.3909	ambiguous	-1.288	Destabilizing	0.992	D	0.443	neutral	None	None	None	None	N
K/T	0.1784	likely_benign	0.1909	benign	-0.989	Destabilizing	0.989	D	0.537	neutral	D	0.57063728	None	None	N
K/V	0.3567	ambiguous	0.403	ambiguous	0.127	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
K/W	0.7139	likely_pathogenic	0.7248	pathogenic	-0.307	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/Y	0.6043	likely_pathogenic	0.6441	pathogenic	0.045	Stabilizing	1.0	D	0.683	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.