TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19329	58210;58211;58212	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
N2AB	17688	53287;53288;53289	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
N2A	16761	50506;50507;50508	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
N2B	10264	31015;31016;31017	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
Novex-1	10389	31390;31391;31392	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
Novex-2	10456	31591;31592;31593	chr2:178594509;178594508;178594507	chr2:179459236;179459235;179459234
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: Fn3-28
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.376
• 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	rs375818281	-0.495	0.001	N	0.107	0.072	0.198526703765	gnomAD-2.1.1	7.14E-06	None	None	None	None	N	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
E/D	rs375818281	-0.495	0.001	N	0.107	0.072	0.198526703765	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs375818281	-0.495	0.001	N	0.107	0.072	0.198526703765	gnomAD-4.0.0	1.36875E-06	None	None	None	None	N	None	5.97979E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs975610705	-0.323	0.722	N	0.489	0.241	0.397838977388	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14732E-04	0	None	0	0	None	0	None	0	0	0
E/Q	rs975610705	-0.323	0.722	N	0.489	0.241	0.397838977388	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
E/Q	rs975610705	-0.323	0.722	N	0.489	0.241	0.397838977388	gnomAD-4.0.0	1.31501E-05	None	None	None	None	N	None	4.82486E-05	0	None	0	0	None	0	0	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	0.3092	likely_benign	0.2417	benign	None	Stabilizing	0.722	D	0.507	neutral	N	0.505976438	None	None	N
E/C	0.9458	likely_pathogenic	0.9245	pathogenic	-0.228	Destabilizing	0.996	D	0.659	neutral	None	None	None	None	N
E/D	0.0925	likely_benign	0.0942	benign	-0.382	Destabilizing	0.001	N	0.107	neutral	N	0.425419499	None	None	N
E/F	0.9468	likely_pathogenic	0.9125	pathogenic	-0.082	Destabilizing	0.987	D	0.575	neutral	None	None	None	None	N
E/G	0.2399	likely_benign	0.1801	benign	-0.098	Destabilizing	0.722	D	0.502	neutral	N	0.443501041	None	None	N
E/H	0.7253	likely_pathogenic	0.6454	pathogenic	0.548	Stabilizing	0.987	D	0.469	neutral	None	None	None	None	N
E/I	0.7324	likely_pathogenic	0.6357	pathogenic	0.196	Stabilizing	0.961	D	0.574	neutral	None	None	None	None	N
E/K	0.3592	ambiguous	0.2391	benign	0.378	Stabilizing	0.722	D	0.509	neutral	N	0.467650124	None	None	N
E/L	0.7253	likely_pathogenic	0.6243	pathogenic	0.196	Stabilizing	0.961	D	0.593	neutral	None	None	None	None	N
E/M	0.7709	likely_pathogenic	0.6838	pathogenic	-0.046	Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
E/N	0.2985	likely_benign	0.2627	benign	0.167	Stabilizing	0.633	D	0.505	neutral	None	None	None	None	N
E/P	0.563	ambiguous	0.4729	ambiguous	0.148	Stabilizing	0.961	D	0.459	neutral	None	None	None	None	N
E/Q	0.2867	likely_benign	0.2225	benign	0.163	Stabilizing	0.722	D	0.489	neutral	N	0.477635044	None	None	N
E/R	0.5742	likely_pathogenic	0.4233	ambiguous	0.598	Stabilizing	0.961	D	0.48	neutral	None	None	None	None	N
E/S	0.2707	likely_benign	0.234	benign	0.032	Stabilizing	0.633	D	0.489	neutral	None	None	None	None	N
E/T	0.3599	ambiguous	0.2999	benign	0.12	Stabilizing	0.775	D	0.487	neutral	None	None	None	None	N
E/V	0.5205	ambiguous	0.4044	ambiguous	0.148	Stabilizing	0.949	D	0.503	neutral	N	0.502109414	None	None	N
E/W	0.9719	likely_pathogenic	0.9492	pathogenic	-0.054	Destabilizing	0.996	D	0.688	prob.neutral	None	None	None	None	N
E/Y	0.8682	likely_pathogenic	0.8083	pathogenic	0.136	Stabilizing	0.987	D	0.539	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.