TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14127	42604;42605;42606	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
N2AB	12486	37681;37682;37683	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
N2A	11559	34900;34901;34902	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
N2B	5062	15409;15410;15411	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
Novex-1	5187	15784;15785;15786	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
Novex-2	5254	15985;15986;15987	chr2:178634402;178634401;178634400	chr2:179499129;179499128;179499127
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-91
• Domain position: 74
• Structural Position: 159
• Q(SASA): 0.5425
• 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	rs750100548	-0.045	0.001	N	0.193	0.029	0.0297737177859	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	5.66E-05	None	0	None	0	0	0
E/D	rs750100548	-0.045	0.001	N	0.193	0.029	0.0297737177859	gnomAD-4.0.0	1.37107E-06	None	None	None	None	N	None	0	0	None	0	2.53024E-05	None	0	0	9.00051E-07	0	0
E/Q	None	None	0.324	N	0.46	0.15	0.132336055621	gnomAD-4.0.0	1.59794E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.42365E-04	0	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	0.2023	likely_benign	0.2157	benign	-0.04	Destabilizing	0.165	N	0.464	neutral	N	0.448825863	None	None	N
E/C	0.8344	likely_pathogenic	0.8857	pathogenic	-0.253	Destabilizing	0.981	D	0.565	neutral	None	None	None	None	N
E/D	0.0972	likely_benign	0.114	benign	-0.35	Destabilizing	0.001	N	0.193	neutral	N	0.442507023	None	None	N
E/F	0.8309	likely_pathogenic	0.8693	pathogenic	0.073	Stabilizing	0.69	D	0.555	neutral	None	None	None	None	N
E/G	0.1821	likely_benign	0.2074	benign	-0.194	Destabilizing	0.324	N	0.533	neutral	N	0.378764009	None	None	N
E/H	0.6244	likely_pathogenic	0.6802	pathogenic	0.687	Stabilizing	0.818	D	0.442	neutral	None	None	None	None	N
E/I	0.6331	likely_pathogenic	0.6842	pathogenic	0.318	Stabilizing	0.241	N	0.561	neutral	None	None	None	None	N
E/K	0.3313	likely_benign	0.3558	ambiguous	0.452	Stabilizing	0.324	N	0.435	neutral	N	0.434449863	None	None	N
E/L	0.5489	ambiguous	0.5855	pathogenic	0.318	Stabilizing	0.001	N	0.345	neutral	None	None	None	None	N
E/M	0.6251	likely_pathogenic	0.6627	pathogenic	0.036	Stabilizing	0.69	D	0.533	neutral	None	None	None	None	N
E/N	0.2601	likely_benign	0.3163	benign	0.029	Stabilizing	0.241	N	0.443	neutral	None	None	None	None	N
E/P	0.7698	likely_pathogenic	0.8095	pathogenic	0.218	Stabilizing	0.818	D	0.491	neutral	None	None	None	None	N
E/Q	0.2468	likely_benign	0.2642	benign	0.074	Stabilizing	0.324	N	0.46	neutral	N	0.444788607	None	None	N
E/R	0.4382	ambiguous	0.476	ambiguous	0.762	Stabilizing	0.69	D	0.441	neutral	None	None	None	None	N
E/S	0.2531	likely_benign	0.2894	benign	-0.081	Destabilizing	0.241	N	0.407	neutral	None	None	None	None	N
E/T	0.4603	ambiguous	0.5029	ambiguous	0.059	Stabilizing	0.388	N	0.499	neutral	None	None	None	None	N
E/V	0.4422	ambiguous	0.4939	ambiguous	0.218	Stabilizing	0.193	N	0.535	neutral	N	0.451648247	None	None	N
E/W	0.9303	likely_pathogenic	0.9471	pathogenic	0.17	Stabilizing	0.981	D	0.639	neutral	None	None	None	None	N
E/Y	0.6709	likely_pathogenic	0.7341	pathogenic	0.314	Stabilizing	0.932	D	0.533	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.