TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35317	106174;106175;106176	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
N2AB	33676	101251;101252;101253	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
N2A	32749	98470;98471;98472	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
N2B	26252	78979;78980;78981	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
Novex-1	26377	79354;79355;79356	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
Novex-2	26444	79555;79556;79557	chr2:178530666;178530665;178530664	chr2:179395393;179395392;179395391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-165
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.1696
• 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
V/A	rs765504674	-1.815	0.003	D	0.412	0.647	0.636883013597	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
V/A	rs765504674	-1.815	0.003	D	0.412	0.647	0.636883013597	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85747E-06	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
V/A	0.5085	ambiguous	0.507	ambiguous	-1.64	Destabilizing	0.003	N	0.412	neutral	D	0.565031179	None	None	N
V/C	0.9322	likely_pathogenic	0.9317	pathogenic	-1.299	Destabilizing	0.955	D	0.699	prob.neutral	None	None	None	None	N
V/D	0.9036	likely_pathogenic	0.9185	pathogenic	-1.26	Destabilizing	0.582	D	0.839	deleterious	D	0.611080143	None	None	N
V/E	0.8551	likely_pathogenic	0.8692	pathogenic	-1.169	Destabilizing	0.648	D	0.822	deleterious	None	None	None	None	N
V/F	0.494	ambiguous	0.5252	ambiguous	-1.107	Destabilizing	0.407	N	0.734	prob.delet.	D	0.535112299	None	None	N
V/G	0.6001	likely_pathogenic	0.5973	pathogenic	-2.052	Highly Destabilizing	0.407	N	0.799	deleterious	D	0.585542031	None	None	N
V/H	0.9659	likely_pathogenic	0.97	pathogenic	-1.543	Destabilizing	0.955	D	0.804	deleterious	None	None	None	None	N
V/I	0.1015	likely_benign	0.1015	benign	-0.57	Destabilizing	0.001	N	0.319	neutral	N	0.46830435	None	None	N
V/K	0.9006	likely_pathogenic	0.9114	pathogenic	-1.289	Destabilizing	0.648	D	0.824	deleterious	None	None	None	None	N
V/L	0.5366	ambiguous	0.542	ambiguous	-0.57	Destabilizing	0.014	N	0.649	neutral	D	0.532074517	None	None	N
V/M	0.3807	ambiguous	0.3733	ambiguous	-0.603	Destabilizing	0.476	N	0.685	prob.neutral	None	None	None	None	N
V/N	0.8361	likely_pathogenic	0.8584	pathogenic	-1.239	Destabilizing	0.849	D	0.833	deleterious	None	None	None	None	N
V/P	0.9075	likely_pathogenic	0.9146	pathogenic	-0.893	Destabilizing	0.849	D	0.825	deleterious	None	None	None	None	N
V/Q	0.8961	likely_pathogenic	0.9088	pathogenic	-1.251	Destabilizing	0.849	D	0.821	deleterious	None	None	None	None	N
V/R	0.8831	likely_pathogenic	0.8986	pathogenic	-0.946	Destabilizing	0.648	D	0.825	deleterious	None	None	None	None	N
V/S	0.762	likely_pathogenic	0.7762	pathogenic	-1.89	Destabilizing	0.313	N	0.804	deleterious	None	None	None	None	N
V/T	0.6082	likely_pathogenic	0.6237	pathogenic	-1.655	Destabilizing	0.206	N	0.689	prob.neutral	None	None	None	None	N
V/W	0.9711	likely_pathogenic	0.9718	pathogenic	-1.332	Destabilizing	0.955	D	0.778	deleterious	None	None	None	None	N
V/Y	0.8933	likely_pathogenic	0.9009	pathogenic	-1.014	Destabilizing	0.648	D	0.715	prob.delet.	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.