TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2711	8356;8357;8358	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
N2AB	2711	8356;8357;8358	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
N2A	2711	8356;8357;8358	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
N2B	2665	8218;8219;8220	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
Novex-1	2665	8218;8219;8220	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
Novex-2	2665	8218;8219;8220	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386
Novex-3	2711	8356;8357;8358	chr2:178770661;178770660;178770659	chr2:179635388;179635387;179635386

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-17
• Domain position: 5
• Structural Position: 5
• Q(SASA): 0.4575
• 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/E	None	None	0.999	D	0.609	0.541	0.617224619168	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62501E-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
K/A	0.6088	likely_pathogenic	0.6171	pathogenic	-0.169	Destabilizing	0.999	D	0.662	neutral	None	None	None	None	N
K/C	0.8942	likely_pathogenic	0.8936	pathogenic	-0.4	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
K/D	0.6713	likely_pathogenic	0.7253	pathogenic	0.163	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/E	0.2966	likely_benign	0.3278	benign	0.208	Stabilizing	0.999	D	0.609	neutral	D	0.615141105	None	None	N
K/F	0.9347	likely_pathogenic	0.944	pathogenic	-0.137	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
K/G	0.6554	likely_pathogenic	0.6713	pathogenic	-0.438	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/H	0.4297	ambiguous	0.4276	ambiguous	-0.68	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
K/I	0.741	likely_pathogenic	0.7724	pathogenic	0.479	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
K/L	0.6859	likely_pathogenic	0.6956	pathogenic	0.479	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/M	0.4856	ambiguous	0.4824	ambiguous	0.231	Stabilizing	1.0	D	0.63	neutral	D	0.619652896	None	None	N
K/N	0.4384	ambiguous	0.4729	ambiguous	-0.024	Destabilizing	1.0	D	0.682	prob.neutral	D	0.657846675	None	None	N
K/P	0.9548	likely_pathogenic	0.9698	pathogenic	0.293	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/Q	0.1921	likely_benign	0.1895	benign	-0.172	Destabilizing	1.0	D	0.659	neutral	N	0.500840217	None	None	N
K/R	0.1029	likely_benign	0.1003	benign	-0.226	Destabilizing	0.999	D	0.539	neutral	N	0.51014397	None	None	N
K/S	0.5703	likely_pathogenic	0.5988	pathogenic	-0.614	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
K/T	0.326	likely_benign	0.3417	ambiguous	-0.396	Destabilizing	1.0	D	0.69	prob.neutral	D	0.546874029	None	None	N
K/V	0.6645	likely_pathogenic	0.6881	pathogenic	0.293	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.9151	likely_pathogenic	0.9151	pathogenic	-0.064	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/Y	0.7974	likely_pathogenic	0.8101	pathogenic	0.252	Stabilizing	1.0	D	0.672	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.