TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14120	42583;42584;42585	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
N2AB	12479	37660;37661;37662	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
N2A	11552	34879;34880;34881	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
N2B	5055	15388;15389;15390	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
Novex-1	5180	15763;15764;15765	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
Novex-2	5247	15964;15965;15966	chr2:178634423;178634422;178634421	chr2:179499150;179499149;179499148
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Ig-91
• Domain position: 67
• Structural Position: 152
• Q(SASA): 0.2305
• 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
G/R	None	None	0.017	D	0.686	0.658	0.726914830792	gnomAD-4.0.0	6.8451E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99703E-07	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
G/A	0.3979	ambiguous	0.365	ambiguous	0.01	Stabilizing	0.003	N	0.431	neutral	D	0.541477845	None	None	N
G/C	0.8205	likely_pathogenic	0.7483	pathogenic	0.02	Stabilizing	0.991	D	0.793	deleterious	None	None	None	None	N
G/D	0.6616	likely_pathogenic	0.4596	ambiguous	-0.849	Destabilizing	0.004	N	0.563	neutral	None	None	None	None	N
G/E	0.8804	likely_pathogenic	0.7855	pathogenic	-0.708	Destabilizing	0.338	N	0.779	deleterious	D	0.706155056	None	None	N
G/F	0.9839	likely_pathogenic	0.9786	pathogenic	-0.161	Destabilizing	0.906	D	0.81	deleterious	None	None	None	None	N
G/H	0.9811	likely_pathogenic	0.9539	pathogenic	-1.208	Destabilizing	0.973	D	0.797	deleterious	None	None	None	None	N
G/I	0.9691	likely_pathogenic	0.9537	pathogenic	0.976	Stabilizing	0.826	D	0.805	deleterious	None	None	None	None	N
G/K	0.9818	likely_pathogenic	0.9588	pathogenic	-0.296	Destabilizing	0.704	D	0.78	deleterious	None	None	None	None	N
G/L	0.9658	likely_pathogenic	0.9488	pathogenic	0.976	Stabilizing	0.826	D	0.788	deleterious	None	None	None	None	N
G/M	0.9652	likely_pathogenic	0.9466	pathogenic	0.761	Stabilizing	0.991	D	0.799	deleterious	None	None	None	None	N
G/N	0.8754	likely_pathogenic	0.7591	pathogenic	-0.409	Destabilizing	0.826	D	0.711	prob.delet.	None	None	None	None	N
G/P	0.9988	likely_pathogenic	0.9979	pathogenic	0.701	Stabilizing	0.906	D	0.791	deleterious	None	None	None	None	N
G/Q	0.9526	likely_pathogenic	0.9126	pathogenic	-0.238	Destabilizing	0.826	D	0.789	deleterious	None	None	None	None	N
G/R	0.9645	likely_pathogenic	0.9272	pathogenic	-0.58	Destabilizing	0.017	N	0.686	prob.neutral	D	0.743778939	None	None	N
G/S	0.4517	ambiguous	0.3391	benign	-0.74	Destabilizing	0.404	N	0.661	neutral	None	None	None	None	N
G/T	0.831	likely_pathogenic	0.7658	pathogenic	-0.476	Destabilizing	0.826	D	0.777	deleterious	None	None	None	None	N
G/V	0.922	likely_pathogenic	0.8842	pathogenic	0.701	Stabilizing	0.642	D	0.795	deleterious	D	0.706155056	None	None	N
G/W	0.9782	likely_pathogenic	0.9593	pathogenic	-0.998	Destabilizing	0.988	D	0.753	deleterious	D	0.743246431	None	None	N
G/Y	0.9724	likely_pathogenic	0.9521	pathogenic	-0.242	Destabilizing	0.973	D	0.813	deleterious	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.