TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27723	83392;83393;83394	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
N2AB	26082	78469;78470;78471	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
N2A	25155	75688;75689;75690	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
N2B	18658	56197;56198;56199	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
Novex-1	18783	56572;56573;56574	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
Novex-2	18850	56773;56774;56775	chr2:178562965;178562964;178562963	chr2:179427692;179427691;179427690
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-141
• Domain position: 48
• Structural Position: 125
• Q(SASA): 0.463
• 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	rs547706181	-0.438	0.011	N	0.194	0.063	0.330331372229	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.59E-05	None	0	None	0	0	0
E/D	rs547706181	-0.438	0.011	N	0.194	0.063	0.330331372229	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93125E-04	None	0	0	0	0	0
E/D	rs547706181	-0.438	0.011	N	0.194	0.063	0.330331372229	1000 genomes	1.99681E-04	None	None	None	None	N	None	0	0	None	None	1E-03	0	None	None	None	0	None
E/D	rs547706181	-0.438	0.011	N	0.194	0.063	0.330331372229	gnomAD-4.0.0	2.05278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6985E-06	0	0
E/K	None	None	0.892	D	0.493	0.339	0.381580015636	gnomAD-4.0.0	1.59157E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85863E-06	0	0
E/Q	rs1223945642	-0.075	0.983	N	0.513	0.318	0.37953744168	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs1223945642	-0.075	0.983	N	0.513	0.318	0.37953744168	gnomAD-4.0.0	3.18313E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86566E-05	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	0.4687	ambiguous	0.5126	ambiguous	-0.628	Destabilizing	0.892	D	0.561	neutral	N	0.491466455	None	None	N
E/C	0.9687	likely_pathogenic	0.9727	pathogenic	-0.351	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
E/D	0.1814	likely_benign	0.2038	benign	-0.761	Destabilizing	0.011	N	0.194	neutral	N	0.472048371	None	None	N
E/F	0.9518	likely_pathogenic	0.9584	pathogenic	0.06	Stabilizing	0.999	D	0.678	prob.neutral	None	None	None	None	N
E/G	0.6405	likely_pathogenic	0.6748	pathogenic	-0.966	Destabilizing	0.892	D	0.567	neutral	N	0.513813898	None	None	N
E/H	0.761	likely_pathogenic	0.7907	pathogenic	0.098	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	N
E/I	0.7467	likely_pathogenic	0.7777	pathogenic	0.283	Stabilizing	0.987	D	0.707	prob.neutral	None	None	None	None	N
E/K	0.5722	likely_pathogenic	0.6244	pathogenic	-0.132	Destabilizing	0.892	D	0.493	neutral	D	0.524437274	None	None	N
E/L	0.7904	likely_pathogenic	0.8183	pathogenic	0.283	Stabilizing	0.987	D	0.701	prob.neutral	None	None	None	None	N
E/M	0.7863	likely_pathogenic	0.8102	pathogenic	0.469	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	N
E/N	0.5118	ambiguous	0.5607	ambiguous	-0.764	Destabilizing	0.95	D	0.547	neutral	None	None	None	None	N
E/P	0.989	likely_pathogenic	0.99	pathogenic	0.001	Stabilizing	0.987	D	0.665	neutral	None	None	None	None	N
E/Q	0.3512	ambiguous	0.3852	ambiguous	-0.624	Destabilizing	0.983	D	0.513	neutral	N	0.487605341	None	None	N
E/R	0.7152	likely_pathogenic	0.7539	pathogenic	0.247	Stabilizing	0.987	D	0.601	neutral	None	None	None	None	N
E/S	0.4654	ambiguous	0.5004	ambiguous	-0.995	Destabilizing	0.916	D	0.492	neutral	None	None	None	None	N
E/T	0.5258	ambiguous	0.56	ambiguous	-0.704	Destabilizing	0.975	D	0.613	neutral	None	None	None	None	N
E/V	0.5335	ambiguous	0.5695	pathogenic	0.001	Stabilizing	0.983	D	0.668	neutral	N	0.48811232	None	None	N
E/W	0.9835	likely_pathogenic	0.987	pathogenic	0.372	Stabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
E/Y	0.9021	likely_pathogenic	0.9168	pathogenic	0.345	Stabilizing	0.999	D	0.651	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.