TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17813	53662;53663;53664	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
N2AB	16172	48739;48740;48741	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
N2A	15245	45958;45959;45960	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
N2B	8748	26467;26468;26469	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
Novex-1	8873	26842;26843;26844	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
Novex-2	8940	27043;27044;27045	chr2:178607165;178607164;178607163	chr2:179471892;179471891;179471890
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Fn3-17
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.7236
• 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
Q/R	rs781026874	0.16	0.492	N	0.504	0.099	0.117506650769	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	5.58E-05	None	0	None	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	0.2727	likely_benign	0.275	benign	-0.155	Destabilizing	0.207	N	0.491	neutral	None	None	None	None	N
Q/C	0.8428	likely_pathogenic	0.872	pathogenic	0.106	Stabilizing	0.981	D	0.519	neutral	None	None	None	None	N
Q/D	0.7721	likely_pathogenic	0.762	pathogenic	0.06	Stabilizing	0.797	D	0.493	neutral	None	None	None	None	N
Q/E	0.2181	likely_benign	0.2034	benign	0.053	Stabilizing	0.286	N	0.458	neutral	N	0.460204076	None	None	N
Q/F	0.7463	likely_pathogenic	0.7533	pathogenic	-0.263	Destabilizing	0.527	D	0.541	neutral	None	None	None	None	N
Q/G	0.5004	ambiguous	0.5186	ambiguous	-0.367	Destabilizing	0.563	D	0.527	neutral	None	None	None	None	N
Q/H	0.5705	likely_pathogenic	0.5483	ambiguous	-0.177	Destabilizing	0.912	D	0.505	neutral	N	0.472055866	None	None	N
Q/I	0.4277	ambiguous	0.4053	ambiguous	0.321	Stabilizing	0.241	N	0.504	neutral	None	None	None	None	N
Q/K	0.3609	ambiguous	0.3032	benign	-0.01	Destabilizing	0.492	N	0.463	neutral	N	0.432169326	None	None	N
Q/L	0.1381	likely_benign	0.1257	benign	0.321	Stabilizing	0.001	N	0.304	neutral	N	0.464263102	None	None	N
Q/M	0.2752	likely_benign	0.2705	benign	0.382	Stabilizing	0.69	D	0.531	neutral	None	None	None	None	N
Q/N	0.4399	ambiguous	0.4604	ambiguous	-0.352	Destabilizing	0.932	D	0.521	neutral	None	None	None	None	N
Q/P	0.2384	likely_benign	0.2352	benign	0.192	Stabilizing	0.912	D	0.549	neutral	N	0.458395922	None	None	N
Q/R	0.4607	ambiguous	0.4133	ambiguous	0.142	Stabilizing	0.492	N	0.504	neutral	N	0.431497322	None	None	N
Q/S	0.2931	likely_benign	0.3298	benign	-0.344	Destabilizing	0.563	D	0.451	neutral	None	None	None	None	N
Q/T	0.2772	likely_benign	0.2707	benign	-0.193	Destabilizing	0.388	N	0.488	neutral	None	None	None	None	N
Q/V	0.2947	likely_benign	0.2797	benign	0.192	Stabilizing	0.008	N	0.34	neutral	None	None	None	None	N
Q/W	0.8627	likely_pathogenic	0.8562	pathogenic	-0.263	Destabilizing	0.981	D	0.551	neutral	None	None	None	None	N
Q/Y	0.6951	likely_pathogenic	0.7049	pathogenic	-0.008	Destabilizing	0.818	D	0.54	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.