TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30600	92023;92024;92025	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
N2AB	28959	87100;87101;87102	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
N2A	28032	84319;84320;84321	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
N2B	21535	64828;64829;64830	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
Novex-1	21660	65203;65204;65205	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
Novex-2	21727	65404;65405;65406	chr2:178550040;178550039;178550038	chr2:179414767;179414766;179414765
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-149
• Domain position: 69
• Structural Position: 157
• Q(SASA): 0.4431
• 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/G	None	None	1.0	N	0.821	0.544	0.633985563651	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1935	likely_benign	0.2082	benign	-1.003	Destabilizing	0.999	D	0.737	prob.delet.	N	0.515857863	None	None	N
E/C	0.8043	likely_pathogenic	0.8213	pathogenic	-0.468	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
E/D	0.315	likely_benign	0.3044	benign	-0.968	Destabilizing	0.999	D	0.551	neutral	D	0.535233058	None	None	N
E/F	0.7335	likely_pathogenic	0.7556	pathogenic	-0.37	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
E/G	0.3895	ambiguous	0.4011	ambiguous	-1.371	Destabilizing	1.0	D	0.821	deleterious	N	0.491176966	None	None	N
E/H	0.4854	ambiguous	0.4993	ambiguous	-0.611	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
E/I	0.2644	likely_benign	0.2843	benign	0.006	Stabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
E/K	0.2296	likely_benign	0.2444	benign	-0.449	Destabilizing	0.999	D	0.679	prob.neutral	N	0.430719036	None	None	N
E/L	0.327	likely_benign	0.3611	ambiguous	0.006	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
E/M	0.3721	ambiguous	0.3995	ambiguous	0.464	Stabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
E/N	0.4179	ambiguous	0.4332	ambiguous	-0.985	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
E/P	0.9909	likely_pathogenic	0.9906	pathogenic	-0.31	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
E/Q	0.158	likely_benign	0.1647	benign	-0.857	Destabilizing	1.0	D	0.723	prob.delet.	N	0.464466251	None	None	N
E/R	0.3873	ambiguous	0.3998	ambiguous	-0.204	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
E/S	0.273	likely_benign	0.29	benign	-1.32	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
E/T	0.2206	likely_benign	0.2426	benign	-1.001	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
E/V	0.1701	likely_benign	0.1812	benign	-0.31	Destabilizing	1.0	D	0.883	deleterious	N	0.441282747	None	None	N
E/W	0.9121	likely_pathogenic	0.9211	pathogenic	-0.037	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
E/Y	0.6752	likely_pathogenic	0.6879	pathogenic	-0.077	Destabilizing	1.0	D	0.907	deleterious	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.