TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19351	58276;58277;58278	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
N2AB	17710	53353;53354;53355	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
N2A	16783	50572;50573;50574	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
N2B	10286	31081;31082;31083	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
Novex-1	10411	31456;31457;31458	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
Novex-2	10478	31657;31658;31659	chr2:178594443;178594442;178594441	chr2:179459170;179459169;179459168
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: Fn3-28
• Domain position: 68
• Structural Position: 99
• Q(SASA): 0.4401
• 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	None	None	0.006	N	0.096	0.161	0.255777322467	gnomAD-4.0.0	3.18562E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.87051E-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	0.3063	likely_benign	0.2478	benign	-0.546	Destabilizing	0.698	D	0.412	neutral	N	0.46449225	None	None	N
E/C	0.966	likely_pathogenic	0.957	pathogenic	-0.065	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	N
E/D	0.4458	ambiguous	0.34	ambiguous	-0.511	Destabilizing	0.006	N	0.096	neutral	N	0.491576635	None	None	N
E/F	0.9799	likely_pathogenic	0.9644	pathogenic	-0.48	Destabilizing	0.978	D	0.559	neutral	None	None	None	None	N
E/G	0.5889	likely_pathogenic	0.4664	ambiguous	-0.776	Destabilizing	0.822	D	0.433	neutral	N	0.501869756	None	None	N
E/H	0.9274	likely_pathogenic	0.8868	pathogenic	-0.506	Destabilizing	0.998	D	0.43	neutral	None	None	None	None	N
E/I	0.7435	likely_pathogenic	0.6441	pathogenic	0.037	Stabilizing	0.915	D	0.467	neutral	None	None	None	None	N
E/K	0.6655	likely_pathogenic	0.5651	pathogenic	0.016	Stabilizing	0.822	D	0.523	neutral	N	0.489081419	None	None	N
E/L	0.8809	likely_pathogenic	0.8159	pathogenic	0.037	Stabilizing	0.754	D	0.475	neutral	None	None	None	None	N
E/M	0.8333	likely_pathogenic	0.7583	pathogenic	0.315	Stabilizing	0.994	D	0.493	neutral	None	None	None	None	N
E/N	0.7099	likely_pathogenic	0.5945	pathogenic	-0.211	Destabilizing	0.915	D	0.434	neutral	None	None	None	None	N
E/P	0.6988	likely_pathogenic	0.6261	pathogenic	-0.136	Destabilizing	0.978	D	0.421	neutral	None	None	None	None	N
E/Q	0.4215	ambiguous	0.3435	ambiguous	-0.178	Destabilizing	0.97	D	0.489	neutral	N	0.474851505	None	None	N
E/R	0.804	likely_pathogenic	0.7478	pathogenic	0.176	Stabilizing	0.978	D	0.453	neutral	None	None	None	None	N
E/S	0.5522	ambiguous	0.4416	ambiguous	-0.419	Destabilizing	0.86	D	0.467	neutral	None	None	None	None	N
E/T	0.5977	likely_pathogenic	0.4813	ambiguous	-0.24	Destabilizing	0.86	D	0.407	neutral	None	None	None	None	N
E/V	0.5481	ambiguous	0.4333	ambiguous	-0.136	Destabilizing	0.032	N	0.256	neutral	N	0.493222476	None	None	N
E/W	0.9944	likely_pathogenic	0.9907	pathogenic	-0.344	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
E/Y	0.9617	likely_pathogenic	0.9338	pathogenic	-0.253	Destabilizing	0.993	D	0.507	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.