TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15417	46474;46475;46476	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
N2AB	13776	41551;41552;41553	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
N2A	12849	38770;38771;38772	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
N2B	6352	19279;19280;19281	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
Novex-1	6477	19654;19655;19656	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
Novex-2	6544	19855;19856;19857	chr2:178620272;178620271;178620270	chr2:179484999;179484998;179484997
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-106
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.6597
• 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	rs993637686	None	0.999	D	0.539	0.478	0.378148810121	gnomAD-4.0.0	1.79013E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.77847E-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	0.2405	likely_benign	0.3519	ambiguous	-0.187	Destabilizing	0.999	D	0.75	deleterious	D	0.541449988	None	None	N
E/C	0.9421	likely_pathogenic	0.9731	pathogenic	0.182	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/D	0.161	likely_benign	0.2084	benign	-0.156	Destabilizing	0.999	D	0.539	neutral	D	0.529888348	None	None	N
E/F	0.9076	likely_pathogenic	0.9577	pathogenic	-0.205	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
E/G	0.1896	likely_benign	0.2947	benign	-0.349	Destabilizing	1.0	D	0.71	prob.delet.	D	0.548742835	None	None	N
E/H	0.7071	likely_pathogenic	0.8216	pathogenic	0.002	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/I	0.6196	likely_pathogenic	0.7698	pathogenic	0.19	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/K	0.2644	likely_benign	0.3778	ambiguous	0.585	Stabilizing	0.999	D	0.723	prob.delet.	D	0.547203503	None	None	N
E/L	0.6149	likely_pathogenic	0.7464	pathogenic	0.19	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/M	0.7004	likely_pathogenic	0.8294	pathogenic	0.286	Stabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
E/N	0.3741	ambiguous	0.5518	ambiguous	0.341	Stabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
E/P	0.3817	ambiguous	0.5032	ambiguous	0.084	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/Q	0.2244	likely_benign	0.306	benign	0.363	Stabilizing	1.0	D	0.695	prob.neutral	D	0.605247753	None	None	N
E/R	0.4268	ambiguous	0.5525	ambiguous	0.654	Stabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
E/S	0.301	likely_benign	0.4489	ambiguous	0.194	Stabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
E/T	0.3964	ambiguous	0.5709	pathogenic	0.331	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
E/V	0.3975	ambiguous	0.5472	ambiguous	0.084	Stabilizing	1.0	D	0.757	deleterious	D	0.572668207	None	None	N
E/W	0.9582	likely_pathogenic	0.9778	pathogenic	-0.116	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
E/Y	0.8256	likely_pathogenic	0.9092	pathogenic	0.033	Stabilizing	1.0	D	0.737	prob.delet.	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.