TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2390	7393;7394;7395	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
N2AB	2390	7393;7394;7395	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
N2A	2390	7393;7394;7395	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
N2B	2344	7255;7256;7257	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
Novex-1	2344	7255;7256;7257	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
Novex-2	2344	7255;7256;7257	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725
Novex-3	2390	7393;7394;7395	chr2:178774000;178773999;178773998	chr2:179638727;179638726;179638725

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-13
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1829
• 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/R	rs777470064	-0.542	0.999	D	0.584	0.606	0.49741755877	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs777470064	-0.542	0.999	D	0.584	0.606	0.49741755877	gnomAD-4.0.0	3.1811E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86541E-05	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	0.9184	likely_pathogenic	0.9223	pathogenic	-0.896	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
K/C	0.8904	likely_pathogenic	0.8955	pathogenic	-0.993	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
K/D	0.9888	likely_pathogenic	0.9899	pathogenic	-0.438	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/E	0.7993	likely_pathogenic	0.808	pathogenic	-0.316	Destabilizing	0.999	D	0.565	neutral	D	0.725171141	None	None	N
K/F	0.9563	likely_pathogenic	0.9574	pathogenic	-0.77	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
K/G	0.9663	likely_pathogenic	0.9687	pathogenic	-1.258	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/H	0.5752	likely_pathogenic	0.6216	pathogenic	-1.709	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/I	0.7894	likely_pathogenic	0.7924	pathogenic	0.048	Stabilizing	1.0	D	0.843	deleterious	D	0.726308531	None	None	N
K/L	0.7435	likely_pathogenic	0.7404	pathogenic	0.048	Stabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
K/M	0.605	likely_pathogenic	0.6084	pathogenic	0.049	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
K/N	0.9361	likely_pathogenic	0.9412	pathogenic	-0.708	Destabilizing	1.0	D	0.716	prob.delet.	D	0.725171141	None	None	N
K/P	0.9967	likely_pathogenic	0.9972	pathogenic	-0.238	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
K/Q	0.4487	ambiguous	0.4644	ambiguous	-0.821	Destabilizing	1.0	D	0.698	prob.neutral	D	0.72658023	None	None	N
K/R	0.1011	likely_benign	0.1002	benign	-0.709	Destabilizing	0.999	D	0.584	neutral	D	0.541736171	None	None	N
K/S	0.9585	likely_pathogenic	0.9618	pathogenic	-1.428	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
K/T	0.8966	likely_pathogenic	0.9061	pathogenic	-1.09	Destabilizing	1.0	D	0.779	deleterious	D	0.72539425	None	None	N
K/V	0.7771	likely_pathogenic	0.7779	pathogenic	-0.238	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/W	0.9331	likely_pathogenic	0.9355	pathogenic	-0.617	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/Y	0.8715	likely_pathogenic	0.875	pathogenic	-0.274	Destabilizing	1.0	D	0.817	deleterious	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.