TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29063	87412;87413;87414	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
N2AB	27422	82489;82490;82491	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
N2A	26495	79708;79709;79710	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
N2B	19998	60217;60218;60219	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
Novex-1	20123	60592;60593;60594	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
Novex-2	20190	60793;60794;60795	chr2:178558167;178558166;178558165	chr2:179422894;179422893;179422892
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: Ig-145
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.3705
• 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/Q	None	None	1.0	N	0.685	0.35	0.193865811164	gnomAD-4.0.0	1.43224E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.57218E-05	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	0.5839	likely_pathogenic	0.5806	pathogenic	-0.198	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
K/C	0.7686	likely_pathogenic	0.7493	pathogenic	-0.319	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/D	0.8724	likely_pathogenic	0.8652	pathogenic	0.054	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
K/E	0.46	ambiguous	0.4349	ambiguous	0.094	Stabilizing	0.999	D	0.575	neutral	N	0.480834773	None	None	N
K/F	0.9031	likely_pathogenic	0.8851	pathogenic	-0.214	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
K/G	0.8196	likely_pathogenic	0.8136	pathogenic	-0.469	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/H	0.3469	ambiguous	0.3246	benign	-0.793	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
K/I	0.5218	ambiguous	0.512	ambiguous	0.454	Stabilizing	1.0	D	0.788	deleterious	N	0.495918868	None	None	N
K/L	0.5534	ambiguous	0.5304	ambiguous	0.454	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/M	0.3542	ambiguous	0.343	ambiguous	0.311	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
K/N	0.7085	likely_pathogenic	0.7071	pathogenic	-0.008	Destabilizing	1.0	D	0.711	prob.delet.	N	0.467156186	None	None	N
K/P	0.957	likely_pathogenic	0.9464	pathogenic	0.267	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/Q	0.1995	likely_benign	0.1919	benign	-0.176	Destabilizing	1.0	D	0.685	prob.neutral	N	0.49678566	None	None	N
K/R	0.0937	likely_benign	0.0886	benign	-0.235	Destabilizing	0.999	D	0.532	neutral	N	0.438102716	None	None	N
K/S	0.6624	likely_pathogenic	0.6645	pathogenic	-0.584	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
K/T	0.2744	likely_benign	0.278	benign	-0.369	Destabilizing	1.0	D	0.753	deleterious	N	0.461534149	None	None	N
K/V	0.4618	ambiguous	0.4439	ambiguous	0.267	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
K/W	0.8698	likely_pathogenic	0.834	pathogenic	-0.144	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
K/Y	0.818	likely_pathogenic	0.7871	pathogenic	0.179	Stabilizing	1.0	D	0.763	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.