TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4904	14935;14936;14937	chr2:178735736;178735735;178735734	chr2:179600463;179600462;179600461
N2AB	4587	13984;13985;13986	chr2:178735736;178735735;178735734	chr2:179600463;179600462;179600461
N2A	3660	11203;11204;11205	chr2:178735736;178735735;178735734	chr2:179600463;179600462;179600461
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-32
• Domain position: 17
• Structural Position: 26
• Q(SASA): 0.5428
• 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	0.801	N	0.307	0.176	0.130388298395	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
K/R	rs1466517766	-0.106	0.012	N	0.178	0.118	0.167679373172	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.56E-05	1.40607E-04
K/R	rs1466517766	-0.106	0.012	N	0.178	0.118	0.167679373172	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/R	rs1466517766	-0.106	0.012	N	0.178	0.118	0.167679373172	gnomAD-4.0.0	3.84316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.78567E-06	0	2.84414E-05

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	0.2021	likely_benign	0.2268	benign	-0.35	Destabilizing	0.525	D	0.385	neutral	None	None	None	None	N
K/C	0.637	likely_pathogenic	0.6661	pathogenic	-0.498	Destabilizing	0.998	D	0.356	neutral	None	None	None	None	N
K/D	0.4047	ambiguous	0.4593	ambiguous	-0.125	Destabilizing	0.842	D	0.383	neutral	None	None	None	None	N
K/E	0.14	likely_benign	0.158	benign	-0.008	Destabilizing	0.801	D	0.307	neutral	N	0.442349198	None	None	N
K/F	0.62	likely_pathogenic	0.6698	pathogenic	0.095	Stabilizing	0.974	D	0.359	neutral	None	None	None	None	N
K/G	0.3082	likely_benign	0.3547	ambiguous	-0.72	Destabilizing	0.842	D	0.372	neutral	None	None	None	None	N
K/H	0.2651	likely_benign	0.2972	benign	-0.976	Destabilizing	0.974	D	0.361	neutral	None	None	None	None	N
K/I	0.2367	likely_benign	0.266	benign	0.606	Stabilizing	0.949	D	0.394	neutral	None	None	None	None	N
K/L	0.2458	likely_benign	0.2779	benign	0.606	Stabilizing	0.728	D	0.366	neutral	None	None	None	None	N
K/M	0.1389	likely_benign	0.1508	benign	0.268	Stabilizing	0.989	D	0.359	neutral	N	0.490476167	None	None	N
K/N	0.2375	likely_benign	0.264	benign	-0.501	Destabilizing	0.801	D	0.325	neutral	N	0.445740561	None	None	N
K/P	0.3435	ambiguous	0.3665	ambiguous	0.318	Stabilizing	0.002	N	0.135	neutral	None	None	None	None	N
K/Q	0.1189	likely_benign	0.1339	benign	-0.494	Destabilizing	0.801	D	0.361	neutral	N	0.451374012	None	None	N
K/R	0.0797	likely_benign	0.0856	benign	-0.665	Destabilizing	0.012	N	0.178	neutral	N	0.447375317	None	None	N
K/S	0.2556	likely_benign	0.2895	benign	-1.05	Destabilizing	0.728	D	0.285	neutral	None	None	None	None	N
K/T	0.0923	likely_benign	0.1033	benign	-0.735	Destabilizing	0.051	N	0.193	neutral	N	0.435597527	None	None	N
K/V	0.2221	likely_benign	0.2489	benign	0.318	Stabilizing	0.728	D	0.359	neutral	None	None	None	None	N
K/W	0.6274	likely_pathogenic	0.6795	pathogenic	0.15	Stabilizing	0.998	D	0.511	neutral	None	None	None	None	N
K/Y	0.4695	ambiguous	0.51	ambiguous	0.417	Stabilizing	0.991	D	0.347	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.