TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24227	72904;72905;72906	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
N2AB	22586	67981;67982;67983	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
N2A	21659	65200;65201;65202	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
N2B	15162	45709;45710;45711	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
Novex-1	15287	46084;46085;46086	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
Novex-2	15354	46285;46286;46287	chr2:178573453;178573452;178573451	chr2:179438180;179438179;179438178
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: Fn3-64
• Domain position: 6
• Structural Position: 6
• Q(SASA): 0.378
• 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	rs1333523637	-0.396	0.016	N	0.19	0.064	0.219573609325	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.49E-05	0
K/Q	rs1333523637	-0.396	0.016	N	0.19	0.064	0.219573609325	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/Q	rs1333523637	-0.396	0.016	N	0.19	0.064	0.219573609325	gnomAD-4.0.0	2.92786E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.35272E-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	0.2069	likely_benign	0.2018	benign	-0.305	Destabilizing	0.25	N	0.441	neutral	None	None	None	None	N
K/C	0.4886	ambiguous	0.4929	ambiguous	-0.193	Destabilizing	0.992	D	0.622	neutral	None	None	None	None	N
K/D	0.489	ambiguous	0.476	ambiguous	-0.207	Destabilizing	0.617	D	0.561	neutral	None	None	None	None	N
K/E	0.1352	likely_benign	0.1274	benign	-0.128	Destabilizing	0.201	N	0.486	neutral	N	0.405540085	None	None	N
K/F	0.7212	likely_pathogenic	0.6866	pathogenic	-0.026	Destabilizing	0.972	D	0.619	neutral	None	None	None	None	N
K/G	0.237	likely_benign	0.2363	benign	-0.655	Destabilizing	0.002	N	0.363	neutral	None	None	None	None	N
K/H	0.3174	likely_benign	0.3131	benign	-1.123	Destabilizing	0.92	D	0.634	neutral	None	None	None	None	N
K/I	0.3135	likely_benign	0.3028	benign	0.59	Stabilizing	0.896	D	0.64	neutral	N	0.492084421	None	None	N
K/L	0.2701	likely_benign	0.2589	benign	0.59	Stabilizing	0.617	D	0.608	neutral	None	None	None	None	N
K/M	0.195	likely_benign	0.1943	benign	0.519	Stabilizing	0.92	D	0.633	neutral	None	None	None	None	N
K/N	0.3541	ambiguous	0.3454	ambiguous	-0.206	Destabilizing	0.549	D	0.498	neutral	N	0.461934873	None	None	N
K/P	0.654	likely_pathogenic	0.6122	pathogenic	0.322	Stabilizing	0.92	D	0.653	neutral	None	None	None	None	N
K/Q	0.1038	likely_benign	0.1019	benign	-0.313	Destabilizing	0.016	N	0.19	neutral	N	0.391418782	None	None	N
K/R	0.0815	likely_benign	0.0779	benign	-0.587	Destabilizing	0.379	N	0.479	neutral	N	0.432649329	None	None	N
K/S	0.2607	likely_benign	0.2595	benign	-0.737	Destabilizing	0.059	N	0.227	neutral	None	None	None	None	N
K/T	0.1381	likely_benign	0.1325	benign	-0.473	Destabilizing	0.379	N	0.562	neutral	N	0.395843167	None	None	N
K/V	0.2331	likely_benign	0.2234	benign	0.322	Stabilizing	0.617	D	0.639	neutral	None	None	None	None	N
K/W	0.7233	likely_pathogenic	0.7043	pathogenic	0.043	Stabilizing	0.992	D	0.649	neutral	None	None	None	None	N
K/Y	0.5858	likely_pathogenic	0.5683	pathogenic	0.324	Stabilizing	0.92	D	0.635	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.