TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4763	14512;14513;14514	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
N2AB	4446	13561;13562;13563	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
N2A	3519	10780;10781;10782	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
N2B	4400	13423;13424;13425	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
Novex-1	4525	13798;13799;13800	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
Novex-2	4592	13999;14000;14001	chr2:178738166;178738165;178738164	chr2:179602893;179602892;179602891
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-30
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.5608
• Predicted PPI site: I

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
Q/K	rs1187967109	0.227	0.679	N	0.213	0.197	0.177238962908	gnomAD-2.1.1	3.18E-05	None	None	None	None	I	None	0	1.17924E-03	None	0	0	None	0	None	0	0	0
Q/L	rs1574049717	None	0.316	N	0.252	0.298	0.493896554345	gnomAD-4.0.0	1.59135E-06	None	None	None	None	I	None	0	2.28655E-05	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
Q/A	0.4247	ambiguous	0.4254	ambiguous	-0.347	Destabilizing	0.037	N	0.146	neutral	None	None	None	None	I
Q/C	0.9549	likely_pathogenic	0.956	pathogenic	0.172	Stabilizing	0.993	D	0.323	neutral	None	None	None	None	I
Q/D	0.7426	likely_pathogenic	0.7807	pathogenic	0.139	Stabilizing	0.932	D	0.189	neutral	None	None	None	None	I
Q/E	0.1389	likely_benign	0.157	benign	0.163	Stabilizing	0.811	D	0.273	neutral	N	0.464614946	None	None	I
Q/F	0.9534	likely_pathogenic	0.95	pathogenic	-0.319	Destabilizing	0.98	D	0.367	neutral	None	None	None	None	I
Q/G	0.594	likely_pathogenic	0.5785	pathogenic	-0.611	Destabilizing	0.584	D	0.364	neutral	None	None	None	None	I
Q/H	0.6141	likely_pathogenic	0.6211	pathogenic	-0.408	Destabilizing	0.991	D	0.295	neutral	N	0.468322411	None	None	I
Q/I	0.8293	likely_pathogenic	0.8321	pathogenic	0.28	Stabilizing	0.037	N	0.208	neutral	None	None	None	None	I
Q/K	0.3073	likely_benign	0.2972	benign	0.012	Stabilizing	0.679	D	0.213	neutral	N	0.465176892	None	None	I
Q/L	0.4334	ambiguous	0.4288	ambiguous	0.28	Stabilizing	0.316	N	0.252	neutral	N	0.468019217	None	None	I
Q/M	0.6555	likely_pathogenic	0.6334	pathogenic	0.553	Stabilizing	0.98	D	0.255	neutral	None	None	None	None	I
Q/N	0.5284	ambiguous	0.5486	ambiguous	-0.418	Destabilizing	0.977	D	0.247	neutral	None	None	None	None	I
Q/P	0.8295	likely_pathogenic	0.833	pathogenic	0.102	Stabilizing	0.912	D	0.345	neutral	N	0.419640354	None	None	I
Q/R	0.3091	likely_benign	0.295	benign	0.129	Stabilizing	0.912	D	0.227	neutral	N	0.467074638	None	None	I
Q/S	0.4269	ambiguous	0.4114	ambiguous	-0.479	Destabilizing	0.584	D	0.221	neutral	None	None	None	None	I
Q/T	0.436	ambiguous	0.4022	ambiguous	-0.272	Destabilizing	0.737	D	0.331	neutral	None	None	None	None	I
Q/V	0.5986	likely_pathogenic	0.5962	pathogenic	0.102	Stabilizing	0.013	N	0.133	neutral	None	None	None	None	I
Q/W	0.9456	likely_pathogenic	0.9381	pathogenic	-0.242	Destabilizing	0.998	D	0.321	neutral	None	None	None	None	I
Q/Y	0.8972	likely_pathogenic	0.9004	pathogenic	-0.009	Destabilizing	0.993	D	0.342	neutral	None	None	None	None	I

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.