TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25658	77197;77198;77199	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
N2AB	24017	72274;72275;72276	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
N2A	23090	69493;69494;69495	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
N2B	16593	50002;50003;50004	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
Novex-1	16718	50377;50378;50379	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
Novex-2	16785	50578;50579;50580	chr2:178569160;178569159;178569158	chr2:179433887;179433886;179433885
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-74
• Domain position: 58
• Structural Position: 89
• Q(SASA): 0.4461
• 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
N/S	None	None	None	N	0.161	0.106	0.0401082797425	gnomAD-4.0.0	1.59233E-06	None	None	None	None	N	None	0	2.2876E-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
N/A	0.1467	likely_benign	0.1777	benign	-0.942	Destabilizing	0.025	N	0.39	neutral	None	None	None	None	N
N/C	0.1303	likely_benign	0.1567	benign	None	Stabilizing	0.667	D	0.475	neutral	None	None	None	None	N
N/D	0.2548	likely_benign	0.2897	benign	-0.422	Destabilizing	0.081	N	0.299	neutral	N	0.511800759	None	None	N
N/E	0.4757	ambiguous	0.5435	ambiguous	-0.247	Destabilizing	0.104	N	0.282	neutral	None	None	None	None	N
N/F	0.384	ambiguous	0.462	ambiguous	-0.639	Destabilizing	0.22	N	0.587	neutral	None	None	None	None	N
N/G	0.2116	likely_benign	0.2569	benign	-1.325	Destabilizing	0.055	N	0.272	neutral	None	None	None	None	N
N/H	0.1281	likely_benign	0.1532	benign	-0.752	Destabilizing	0.001	N	0.303	neutral	N	0.494484434	None	None	N
N/I	0.1331	likely_benign	0.1504	benign	0.063	Stabilizing	0.096	N	0.451	neutral	N	0.465462847	None	None	N
N/K	0.3112	likely_benign	0.3696	ambiguous	0.124	Stabilizing	0.042	N	0.295	neutral	N	0.482728645	None	None	N
N/L	0.1121	likely_benign	0.1265	benign	0.063	Stabilizing	0.025	N	0.371	neutral	None	None	None	None	N
N/M	0.1489	likely_benign	0.1715	benign	0.292	Stabilizing	0.005	N	0.394	neutral	None	None	None	None	N
N/P	0.2675	likely_benign	0.3257	benign	-0.243	Destabilizing	0.364	N	0.516	neutral	None	None	None	None	N
N/Q	0.2944	likely_benign	0.3562	ambiguous	-0.438	Destabilizing	0.22	N	0.305	neutral	None	None	None	None	N
N/R	0.3604	ambiguous	0.4272	ambiguous	0.027	Stabilizing	0.22	N	0.273	neutral	None	None	None	None	N
N/S	0.0842	likely_benign	0.0943	benign	-0.814	Destabilizing	None	N	0.161	neutral	N	0.502141125	None	None	N
N/T	0.0701	likely_benign	0.0765	benign	-0.421	Destabilizing	None	N	0.155	neutral	N	0.346062133	None	None	N
N/V	0.1386	likely_benign	0.1537	benign	-0.243	Destabilizing	0.055	N	0.388	neutral	None	None	None	None	N
N/W	0.7119	likely_pathogenic	0.7696	pathogenic	-0.389	Destabilizing	0.958	D	0.498	neutral	None	None	None	None	N
N/Y	0.1283	likely_benign	0.1514	benign	-0.107	Destabilizing	0.175	N	0.589	neutral	N	0.470489276	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.