TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20625	62098;62099;62100	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
N2AB	18984	57175;57176;57177	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
N2A	18057	54394;54395;54396	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
N2B	11560	34903;34904;34905	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
Novex-1	11685	35278;35279;35280	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
Novex-2	11752	35479;35480;35481	chr2:178589852;178589851;178589850	chr2:179454579;179454578;179454577
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: Fn3-37
• Domain position: 57
• Structural Position: 88
• Q(SASA): 0.4197
• 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	rs2049837055	None	0.193	N	0.459	0.205	0.229924730088	gnomAD-4.0.0	1.36869E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79918E-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	0.6566	likely_pathogenic	0.7318	pathogenic	-0.047	Destabilizing	0.388	N	0.454	neutral	None	None	None	None	N
K/C	0.8696	likely_pathogenic	0.8878	pathogenic	-0.529	Destabilizing	0.981	D	0.585	neutral	None	None	None	None	N
K/D	0.7645	likely_pathogenic	0.8095	pathogenic	-0.056	Destabilizing	0.241	N	0.445	neutral	None	None	None	None	N
K/E	0.411	ambiguous	0.4728	ambiguous	0.003	Stabilizing	0.193	N	0.459	neutral	N	0.468644627	None	None	N
K/F	0.961	likely_pathogenic	0.9685	pathogenic	-0.107	Destabilizing	0.818	D	0.562	neutral	None	None	None	None	N
K/G	0.6005	likely_pathogenic	0.6697	pathogenic	-0.282	Destabilizing	0.388	N	0.467	neutral	None	None	None	None	N
K/H	0.516	ambiguous	0.5441	ambiguous	-0.363	Destabilizing	0.818	D	0.51	neutral	None	None	None	None	N
K/I	0.8449	likely_pathogenic	0.8718	pathogenic	0.51	Stabilizing	0.773	D	0.563	neutral	N	0.487230388	None	None	N
K/L	0.7552	likely_pathogenic	0.804	pathogenic	0.51	Stabilizing	0.388	N	0.487	neutral	None	None	None	None	N
K/M	0.6555	likely_pathogenic	0.7018	pathogenic	-0.054	Destabilizing	0.981	D	0.505	neutral	None	None	None	None	N
K/N	0.6114	likely_pathogenic	0.6485	pathogenic	-0.171	Destabilizing	0.003	N	0.147	neutral	N	0.411367192	None	None	N
K/P	0.8648	likely_pathogenic	0.8829	pathogenic	0.352	Stabilizing	0.818	D	0.497	neutral	None	None	None	None	N
K/Q	0.2332	likely_benign	0.2634	benign	-0.193	Destabilizing	0.324	N	0.474	neutral	N	0.473666445	None	None	N
K/R	0.1063	likely_benign	0.1071	benign	-0.134	Destabilizing	0.001	N	0.257	neutral	N	0.43626285	None	None	N
K/S	0.6121	likely_pathogenic	0.6769	pathogenic	-0.599	Destabilizing	0.388	N	0.428	neutral	None	None	None	None	N
K/T	0.4339	ambiguous	0.5057	ambiguous	-0.374	Destabilizing	0.324	N	0.445	neutral	N	0.397701675	None	None	N
K/V	0.7541	likely_pathogenic	0.7945	pathogenic	0.352	Stabilizing	0.69	D	0.472	neutral	None	None	None	None	N
K/W	0.9397	likely_pathogenic	0.9459	pathogenic	-0.18	Destabilizing	0.981	D	0.654	neutral	None	None	None	None	N
K/Y	0.8683	likely_pathogenic	0.8777	pathogenic	0.169	Stabilizing	0.818	D	0.549	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.