TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24264	73015;73016;73017	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
N2AB	22623	68092;68093;68094	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
N2A	21696	65311;65312;65313	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
N2B	15199	45820;45821;45822	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
Novex-1	15324	46195;46196;46197	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
Novex-2	15391	46396;46397;46398	chr2:178573342;178573341;178573340	chr2:179438069;179438068;179438067
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: 43
• Structural Position: 50
• Q(SASA): 0.3962
• 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/I	rs745449959	0.54	0.018	N	0.488	0.226	0.345859378078	gnomAD-2.1.1	5.17E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.09E-05	0
K/I	rs745449959	0.54	0.018	N	0.488	0.226	0.345859378078	gnomAD-4.0.0	7.18776E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.27754E-07	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	0.5631	ambiguous	0.5121	ambiguous	-0.559	Destabilizing	0.775	D	0.513	neutral	None	None	None	None	N
K/C	0.7908	likely_pathogenic	0.7869	pathogenic	-0.568	Destabilizing	0.996	D	0.715	prob.delet.	None	None	None	None	N
K/D	0.9048	likely_pathogenic	0.8692	pathogenic	-0.036	Destabilizing	0.923	D	0.527	neutral	None	None	None	None	N
K/E	0.4212	ambiguous	0.3454	ambiguous	0.061	Stabilizing	0.722	D	0.463	neutral	N	0.47102639	None	None	N
K/F	0.8969	likely_pathogenic	0.864	pathogenic	-0.312	Destabilizing	0.923	D	0.69	prob.neutral	None	None	None	None	N
K/G	0.6924	likely_pathogenic	0.6359	pathogenic	-0.899	Destabilizing	0.923	D	0.583	neutral	None	None	None	None	N
K/H	0.4663	ambiguous	0.431	ambiguous	-1.156	Destabilizing	0.989	D	0.544	neutral	None	None	None	None	N
K/I	0.5252	ambiguous	0.4815	ambiguous	0.309	Stabilizing	0.018	N	0.488	neutral	N	0.467623029	None	None	N
K/L	0.5479	ambiguous	0.5067	ambiguous	0.309	Stabilizing	0.372	N	0.59	neutral	None	None	None	None	N
K/M	0.3849	ambiguous	0.344	ambiguous	0.112	Stabilizing	0.979	D	0.544	neutral	None	None	None	None	N
K/N	0.8041	likely_pathogenic	0.7383	pathogenic	-0.387	Destabilizing	0.901	D	0.455	neutral	N	0.475789784	None	None	N
K/P	0.9381	likely_pathogenic	0.916	pathogenic	0.05	Stabilizing	0.961	D	0.549	neutral	None	None	None	None	N
K/Q	0.2114	likely_benign	0.1873	benign	-0.453	Destabilizing	0.901	D	0.493	neutral	N	0.49945022	None	None	N
K/R	0.0748	likely_benign	0.0717	benign	-0.495	Destabilizing	0.008	N	0.198	neutral	N	0.485158449	None	None	N
K/S	0.711	likely_pathogenic	0.6515	pathogenic	-1.026	Destabilizing	0.775	D	0.47	neutral	None	None	None	None	N
K/T	0.441	ambiguous	0.3935	ambiguous	-0.725	Destabilizing	0.722	D	0.498	neutral	N	0.505859008	None	None	N
K/V	0.4867	ambiguous	0.4645	ambiguous	0.05	Stabilizing	0.372	N	0.597	neutral	None	None	None	None	N
K/W	0.8655	likely_pathogenic	0.8433	pathogenic	-0.194	Destabilizing	0.996	D	0.706	prob.neutral	None	None	None	None	N
K/Y	0.8002	likely_pathogenic	0.7613	pathogenic	0.087	Stabilizing	0.961	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.