TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19693	59302;59303;59304	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
N2AB	18052	54379;54380;54381	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
N2A	17125	51598;51599;51600	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
N2B	10628	32107;32108;32109	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
Novex-1	10753	32482;32483;32484	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
Novex-2	10820	32683;32684;32685	chr2:178593042;178593041;178593040	chr2:179457769;179457768;179457767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-31
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2165
• 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
T/A	rs1218974177	None	0.948	N	0.441	0.321	0.397540356873	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93723E-04	None	0	0	0	0	0
T/A	rs1218974177	None	0.948	N	0.441	0.321	0.397540356873	gnomAD-4.0.0	6.57393E-06	None	None	None	None	N	None	0	0	None	0	1.93723E-04	None	0	0	0	0	0
T/I	None	None	0.998	N	0.662	0.487	0.619139198567	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85946E-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
T/A	0.2473	likely_benign	0.2152	benign	-0.462	Destabilizing	0.948	D	0.441	neutral	N	0.481540683	None	None	N
T/C	0.7901	likely_pathogenic	0.7686	pathogenic	-0.469	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
T/D	0.7256	likely_pathogenic	0.6706	pathogenic	-1.445	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
T/E	0.8344	likely_pathogenic	0.7867	pathogenic	-1.466	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
T/F	0.8137	likely_pathogenic	0.7556	pathogenic	-0.943	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
T/G	0.327	likely_benign	0.3296	benign	-0.656	Destabilizing	0.992	D	0.535	neutral	None	None	None	None	N
T/H	0.6619	likely_pathogenic	0.6054	pathogenic	-1.144	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
T/I	0.8687	likely_pathogenic	0.8167	pathogenic	-0.044	Destabilizing	0.998	D	0.662	neutral	N	0.511610355	None	None	N
T/K	0.6696	likely_pathogenic	0.588	pathogenic	-0.65	Destabilizing	0.997	D	0.622	neutral	N	0.487376807	None	None	N
T/L	0.5095	ambiguous	0.4253	ambiguous	-0.044	Destabilizing	0.996	D	0.555	neutral	None	None	None	None	N
T/M	0.4318	ambiguous	0.3465	ambiguous	0.474	Stabilizing	1.0	D	0.625	neutral	None	None	None	None	N
T/N	0.3226	likely_benign	0.2861	benign	-0.849	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
T/P	0.7985	likely_pathogenic	0.7388	pathogenic	-0.154	Destabilizing	0.998	D	0.66	neutral	N	0.516383295	None	None	N
T/Q	0.6412	likely_pathogenic	0.588	pathogenic	-1.189	Destabilizing	0.999	D	0.654	neutral	None	None	None	None	N
T/R	0.5876	likely_pathogenic	0.4945	ambiguous	-0.281	Destabilizing	0.998	D	0.667	neutral	N	0.470905167	None	None	N
T/S	0.1394	likely_benign	0.1399	benign	-0.849	Destabilizing	0.775	D	0.227	neutral	N	0.46891956	None	None	N
T/V	0.6795	likely_pathogenic	0.6118	pathogenic	-0.154	Destabilizing	0.996	D	0.52	neutral	None	None	None	None	N
T/W	0.9571	likely_pathogenic	0.9389	pathogenic	-0.994	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
T/Y	0.803	likely_pathogenic	0.756	pathogenic	-0.638	Destabilizing	1.0	D	0.698	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.