TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18061	54406;54407;54408	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
N2AB	16420	49483;49484;49485	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
N2A	15493	46702;46703;46704	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
N2B	8996	27211;27212;27213	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
Novex-1	9121	27586;27587;27588	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
Novex-2	9188	27787;27788;27789	chr2:178604996;178604995;178604994	chr2:179469723;179469722;179469721
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-114
• Domain position: 94
• Structural Position: 175
• Q(SASA): 0.363
• 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
E/D	rs757026449	-1.092	0.993	N	0.331	0.202	0.292423486923	gnomAD-2.1.1	8.49E-06	None	None	None	None	N	None	0	5.99E-05	None	0	0	None	0	None	0	0	0
E/D	rs757026449	-1.092	0.993	N	0.331	0.202	0.292423486923	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/D	rs757026449	-1.092	0.993	N	0.331	0.202	0.292423486923	gnomAD-4.0.0	3.93583E-06	None	None	None	None	N	None	0	5.19409E-05	None	0	0	None	0	0	0	0	0
E/K	None	None	0.979	N	0.322	0.338	0.393471546983	gnomAD-4.0.0	1.63943E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94473E-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
E/A	0.322	likely_benign	0.45	ambiguous	-0.757	Destabilizing	0.906	D	0.329	neutral	N	0.497906821	None	None	N
E/C	0.9379	likely_pathogenic	0.9662	pathogenic	-0.664	Destabilizing	1.0	D	0.467	neutral	None	None	None	None	N
E/D	0.2105	likely_benign	0.2761	benign	-1.561	Destabilizing	0.993	D	0.331	neutral	N	0.468240061	None	None	N
E/F	0.8671	likely_pathogenic	0.9243	pathogenic	0.022	Stabilizing	0.991	D	0.479	neutral	None	None	None	None	N
E/G	0.6002	likely_pathogenic	0.7138	pathogenic	-1.19	Destabilizing	0.979	D	0.411	neutral	N	0.508725017	None	None	N
E/H	0.72	likely_pathogenic	0.8114	pathogenic	-0.401	Destabilizing	0.999	D	0.356	neutral	None	None	None	None	N
E/I	0.448	ambiguous	0.5894	pathogenic	0.454	Stabilizing	0.939	D	0.465	neutral	None	None	None	None	N
E/K	0.5447	ambiguous	0.6379	pathogenic	-1.322	Destabilizing	0.979	D	0.322	neutral	N	0.472451016	None	None	N
E/L	0.6056	likely_pathogenic	0.7268	pathogenic	0.454	Stabilizing	0.039	N	0.31	neutral	None	None	None	None	N
E/M	0.5997	likely_pathogenic	0.7256	pathogenic	0.964	Stabilizing	0.546	D	0.295	neutral	None	None	None	None	N
E/N	0.4429	ambiguous	0.5969	pathogenic	-1.765	Destabilizing	0.999	D	0.347	neutral	None	None	None	None	N
E/P	0.9916	likely_pathogenic	0.9963	pathogenic	0.071	Stabilizing	0.999	D	0.407	neutral	None	None	None	None	N
E/Q	0.2937	likely_benign	0.3732	ambiguous	-1.52	Destabilizing	0.979	D	0.381	neutral	N	0.483476086	None	None	N
E/R	0.6869	likely_pathogenic	0.7672	pathogenic	-0.998	Destabilizing	0.995	D	0.338	neutral	None	None	None	None	N
E/S	0.3926	ambiguous	0.5298	ambiguous	-2.174	Highly Destabilizing	0.984	D	0.281	neutral	None	None	None	None	N
E/T	0.3513	ambiguous	0.4862	ambiguous	-1.814	Destabilizing	0.984	D	0.329	neutral	None	None	None	None	N
E/V	0.2906	likely_benign	0.4022	ambiguous	0.071	Stabilizing	0.828	D	0.381	neutral	N	0.482689439	None	None	N
E/W	0.9657	likely_pathogenic	0.9805	pathogenic	0.131	Stabilizing	1.0	D	0.512	neutral	None	None	None	None	N
E/Y	0.8281	likely_pathogenic	0.9034	pathogenic	0.201	Stabilizing	0.999	D	0.46	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.