TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4640	14143;14144;14145	chr2:178739315;178739314;178739313	chr2:179604042;179604041;179604040
N2AB	4323	13192;13193;13194	chr2:178739315;178739314;178739313	chr2:179604042;179604041;179604040
N2A	None	None	chr2:None	chr2:None
N2B	4277	13054;13055;13056	chr2:178739315;178739314;178739313	chr2:179604042;179604041;179604040
Novex-1	4402	13429;13430;13431	chr2:178739315;178739314;178739313	chr2:179604042;179604041;179604040
Novex-2	4469	13630;13631;13632	chr2:178739315;178739314;178739313	chr2:179604042;179604041;179604040
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-29
• Domain position: 35
• Structural Position: 51
• Q(SASA): 0.3035
• 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	rs1441462753	-0.969	None	N	0.169	0.071	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
E/G	rs1441462753	-0.969	None	N	0.169	0.071	None	gnomAD-4.0.0	4.10582E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49766E-06	0	1.65684E-05
E/K	rs1156910102	None	None	N	0.134	0.065	None	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	5.65291E-05	0	None	0	0	None	0	0	0	0	0
E/Q	rs1156910102	-0.441	0.003	N	0.171	0.064	None	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/Q	rs1156910102	-0.441	0.003	N	0.171	0.064	None	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43303E-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	0.1614	likely_benign	0.1658	benign	-0.479	Destabilizing	0.019	N	0.284	neutral	N	0.466495205	None	None	N
E/C	0.6463	likely_pathogenic	0.6601	pathogenic	-0.267	Destabilizing	0.958	D	0.407	neutral	None	None	None	None	N
E/D	0.1553	likely_benign	0.1617	benign	-0.403	Destabilizing	None	N	0.164	neutral	N	0.430491162	None	None	N
E/F	0.7179	likely_pathogenic	0.7338	pathogenic	-0.119	Destabilizing	0.859	D	0.441	neutral	None	None	None	None	N
E/G	0.0856	likely_benign	0.0848	benign	-0.712	Destabilizing	None	N	0.169	neutral	N	0.442523146	None	None	N
E/H	0.3225	likely_benign	0.329	benign	0.148	Stabilizing	0.667	D	0.252	neutral	None	None	None	None	N
E/I	0.5138	ambiguous	0.5476	ambiguous	0.117	Stabilizing	0.667	D	0.479	neutral	None	None	None	None	N
E/K	0.0942	likely_benign	0.0914	benign	0.177	Stabilizing	None	N	0.134	neutral	N	0.449879835	None	None	N
E/L	0.3543	ambiguous	0.3807	ambiguous	0.117	Stabilizing	0.22	N	0.447	neutral	None	None	None	None	N
E/M	0.4273	ambiguous	0.4457	ambiguous	0.131	Stabilizing	0.667	D	0.414	neutral	None	None	None	None	N
E/N	0.2037	likely_benign	0.2091	benign	-0.303	Destabilizing	None	N	0.13	neutral	None	None	None	None	N
E/P	0.7634	likely_pathogenic	0.7998	pathogenic	-0.061	Destabilizing	0.364	N	0.415	neutral	None	None	None	None	N
E/Q	0.0924	likely_benign	0.0918	benign	-0.225	Destabilizing	0.003	N	0.171	neutral	N	0.454264288	None	None	N
E/R	0.1361	likely_benign	0.1341	benign	0.486	Stabilizing	0.124	N	0.187	neutral	None	None	None	None	N
E/S	0.1807	likely_benign	0.188	benign	-0.46	Destabilizing	0.002	N	0.143	neutral	None	None	None	None	N
E/T	0.3141	likely_benign	0.3419	ambiguous	-0.26	Destabilizing	0.055	N	0.349	neutral	None	None	None	None	N
E/V	0.3494	ambiguous	0.3784	ambiguous	-0.061	Destabilizing	0.175	N	0.469	neutral	D	0.549454913	None	None	N
E/W	0.7858	likely_pathogenic	0.8122	pathogenic	0.11	Stabilizing	0.958	D	0.428	neutral	None	None	None	None	N
E/Y	0.5344	ambiguous	0.5533	ambiguous	0.139	Stabilizing	0.859	D	0.434	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.