TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10014	30265;30266;30267	chr2:178704330;178704329;178704328	chr2:179569057;179569056;179569055
N2AB	9697	29314;29315;29316	chr2:178704330;178704329;178704328	chr2:179569057;179569056;179569055
N2A	8770	26533;26534;26535	chr2:178704330;178704329;178704328	chr2:179569057;179569056;179569055
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-85
• Domain position: 26
• Structural Position: 41
• Q(SASA): 0.5783
• 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/L	rs745949099	0.002	0.76	None	0.488	0.1	0.614608367865	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
V/L	rs745949099	0.002	0.76	None	0.488	0.1	0.614608367865	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/L	rs745949099	0.002	0.76	None	0.488	0.1	0.614608367865	gnomAD-4.0.0	3.84235E-06	None	None	None	None	N	None	5.07322E-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	0.6534	likely_pathogenic	0.6037	pathogenic	-1.681	Destabilizing	0.939	D	0.492	neutral	None	None	None	None	N
V/C	0.9614	likely_pathogenic	0.9528	pathogenic	-1.15	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	N
V/D	0.9399	likely_pathogenic	0.9077	pathogenic	-1.591	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
V/E	0.8028	likely_pathogenic	0.7445	pathogenic	-1.482	Destabilizing	0.997	D	0.721	prob.delet.	None	None	None	None	N
V/F	0.5071	ambiguous	0.429	ambiguous	-1.111	Destabilizing	0.986	D	0.68	prob.neutral	None	None	None	None	N
V/G	0.8632	likely_pathogenic	0.8124	pathogenic	-2.114	Highly Destabilizing	0.997	D	0.733	prob.delet.	None	None	None	None	N
V/H	0.9402	likely_pathogenic	0.9097	pathogenic	-1.652	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
V/I	0.0953	likely_benign	0.1026	benign	-0.542	Destabilizing	0.046	N	0.262	neutral	None	None	None	None	N
V/K	0.8302	likely_pathogenic	0.7684	pathogenic	-1.348	Destabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
V/L	0.4646	ambiguous	0.438	ambiguous	-0.542	Destabilizing	0.76	D	0.488	neutral	None	None	None	None	N
V/M	0.3792	ambiguous	0.3659	ambiguous	-0.468	Destabilizing	0.986	D	0.669	neutral	None	None	None	None	N
V/N	0.8895	likely_pathogenic	0.8512	pathogenic	-1.349	Destabilizing	0.998	D	0.76	deleterious	None	None	None	None	N
V/P	0.9812	likely_pathogenic	0.9765	pathogenic	-0.888	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	N
V/Q	0.8179	likely_pathogenic	0.7595	pathogenic	-1.355	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
V/R	0.7949	likely_pathogenic	0.7233	pathogenic	-0.999	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
V/S	0.7962	likely_pathogenic	0.7424	pathogenic	-1.963	Destabilizing	0.993	D	0.721	prob.delet.	None	None	None	None	N
V/T	0.6556	likely_pathogenic	0.625	pathogenic	-1.715	Destabilizing	0.953	D	0.617	neutral	None	None	None	None	N
V/W	0.9823	likely_pathogenic	0.9731	pathogenic	-1.42	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
V/Y	0.9119	likely_pathogenic	0.8777	pathogenic	-1.067	Destabilizing	0.998	D	0.691	prob.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.