TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16162	48709;48710;48711	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
N2AB	14521	43786;43787;43788	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
N2A	13594	41005;41006;41007	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
N2B	7097	21514;21515;21516	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
Novex-1	7222	21889;21890;21891	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
Novex-2	7289	22090;22091;22092	chr2:178615461;178615460;178615459	chr2:179480188;179480187;179480186
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-5
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1997
• 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/I	rs1240591275	-0.708	None	N	0.265	0.073	0.216624796971	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.28E-05	None	0	0	0
V/L	rs1240591275	None	None	N	0.281	0.036	0.166414681773	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs1240591275	None	None	N	0.281	0.036	0.166414681773	gnomAD-4.0.0	3.04565E-06	None	None	None	None	N	None	5.24494E-05	0	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
V/A	0.8695	likely_pathogenic	0.8424	pathogenic	-1.864	Destabilizing	0.052	N	0.712	prob.delet.	N	0.5113697	None	None	N
V/C	0.9338	likely_pathogenic	0.9292	pathogenic	-1.65	Destabilizing	0.935	D	0.73	prob.delet.	None	None	None	None	N
V/D	0.9941	likely_pathogenic	0.9911	pathogenic	-2.435	Highly Destabilizing	0.741	D	0.813	deleterious	D	0.641084948	None	None	N
V/E	0.9833	likely_pathogenic	0.9763	pathogenic	-2.336	Highly Destabilizing	0.555	D	0.777	deleterious	None	None	None	None	N
V/F	0.8316	likely_pathogenic	0.7225	pathogenic	-1.311	Destabilizing	0.188	N	0.781	deleterious	N	0.487233112	None	None	N
V/G	0.9059	likely_pathogenic	0.8831	pathogenic	-2.29	Highly Destabilizing	0.484	N	0.795	deleterious	D	0.642401848	None	None	N
V/H	0.9952	likely_pathogenic	0.9929	pathogenic	-2.004	Highly Destabilizing	0.935	D	0.797	deleterious	None	None	None	None	N
V/I	0.0993	likely_benign	0.0923	benign	-0.731	Destabilizing	None	N	0.265	neutral	N	0.48873291	None	None	N
V/K	0.9866	likely_pathogenic	0.9809	pathogenic	-1.538	Destabilizing	0.555	D	0.769	deleterious	None	None	None	None	N
V/L	0.3095	likely_benign	0.2288	benign	-0.731	Destabilizing	None	N	0.281	neutral	N	0.362882553	None	None	N
V/M	0.5655	likely_pathogenic	0.47	ambiguous	-0.776	Destabilizing	0.235	N	0.711	prob.delet.	None	None	None	None	N
V/N	0.9795	likely_pathogenic	0.9745	pathogenic	-1.605	Destabilizing	0.791	D	0.82	deleterious	None	None	None	None	N
V/P	0.8383	likely_pathogenic	0.8207	pathogenic	-1.078	Destabilizing	0.791	D	0.776	deleterious	None	None	None	None	N
V/Q	0.9816	likely_pathogenic	0.9744	pathogenic	-1.652	Destabilizing	0.791	D	0.779	deleterious	None	None	None	None	N
V/R	0.9806	likely_pathogenic	0.9711	pathogenic	-1.211	Destabilizing	0.555	D	0.821	deleterious	None	None	None	None	N
V/S	0.9647	likely_pathogenic	0.9561	pathogenic	-2.156	Highly Destabilizing	0.555	D	0.779	deleterious	None	None	None	None	N
V/T	0.8537	likely_pathogenic	0.8416	pathogenic	-1.934	Destabilizing	0.149	N	0.735	prob.delet.	None	None	None	None	N
V/W	0.9955	likely_pathogenic	0.9906	pathogenic	-1.688	Destabilizing	0.935	D	0.797	deleterious	None	None	None	None	N
V/Y	0.9851	likely_pathogenic	0.9747	pathogenic	-1.345	Destabilizing	0.555	D	0.768	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.