TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18738	56437;56438;56439	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
N2AB	17097	51514;51515;51516	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
N2A	16170	48733;48734;48735	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
N2B	9673	29242;29243;29244	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
Novex-1	9798	29617;29618;29619	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
Novex-2	9865	29818;29819;29820	chr2:178599689;178599688;178599687	chr2:179464416;179464415;179464414
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-116
• Domain position: 51
• Structural Position: 121
• Q(SASA): 0.1946
• 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/G	rs777956655	-1.767	0.928	N	0.721	0.631	None	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.78E-05	0
V/G	rs777956655	-1.767	0.928	N	0.721	0.631	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/G	rs777956655	-1.767	0.928	N	0.721	0.631	None	gnomAD-4.0.0	8.97572E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.67667E-05	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	0.4513	ambiguous	0.4509	ambiguous	-2.07	Highly Destabilizing	0.645	D	0.415	neutral	D	0.532502184	None	None	N
V/C	0.7362	likely_pathogenic	0.7176	pathogenic	-1.568	Destabilizing	0.995	D	0.647	neutral	None	None	None	None	N
V/D	0.7594	likely_pathogenic	0.7711	pathogenic	-2.992	Highly Destabilizing	0.928	D	0.74	deleterious	N	0.503017478	None	None	N
V/E	0.5989	likely_pathogenic	0.6069	pathogenic	-2.809	Highly Destabilizing	0.945	D	0.683	prob.neutral	None	None	None	None	N
V/F	0.2664	likely_benign	0.2537	benign	-1.331	Destabilizing	0.864	D	0.679	prob.neutral	N	0.480206494	None	None	N
V/G	0.5378	ambiguous	0.5257	ambiguous	-2.568	Highly Destabilizing	0.928	D	0.721	prob.delet.	N	0.493609729	None	None	N
V/H	0.7831	likely_pathogenic	0.7789	pathogenic	-2.521	Highly Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
V/I	0.0665	likely_benign	0.065	benign	-0.689	Destabilizing	0.002	N	0.201	neutral	N	0.425257288	None	None	N
V/K	0.5851	likely_pathogenic	0.6051	pathogenic	-1.908	Destabilizing	0.945	D	0.686	prob.neutral	None	None	None	None	N
V/L	0.2131	likely_benign	0.2229	benign	-0.689	Destabilizing	0.114	N	0.372	neutral	N	0.495655949	None	None	N
V/M	0.1793	likely_benign	0.1849	benign	-0.595	Destabilizing	0.894	D	0.596	neutral	None	None	None	None	N
V/N	0.5696	likely_pathogenic	0.5735	pathogenic	-2.146	Highly Destabilizing	0.981	D	0.733	prob.delet.	None	None	None	None	N
V/P	0.9366	likely_pathogenic	0.9358	pathogenic	-1.123	Destabilizing	0.981	D	0.706	prob.neutral	None	None	None	None	N
V/Q	0.5751	likely_pathogenic	0.5741	pathogenic	-2.032	Highly Destabilizing	0.981	D	0.689	prob.neutral	None	None	None	None	N
V/R	0.5493	ambiguous	0.5429	ambiguous	-1.657	Destabilizing	0.945	D	0.73	prob.delet.	None	None	None	None	N
V/S	0.524	ambiguous	0.5291	ambiguous	-2.656	Highly Destabilizing	0.945	D	0.671	neutral	None	None	None	None	N
V/T	0.3392	likely_benign	0.3604	ambiguous	-2.35	Highly Destabilizing	0.707	D	0.507	neutral	None	None	None	None	N
V/W	0.8569	likely_pathogenic	0.8412	pathogenic	-1.972	Destabilizing	0.995	D	0.681	prob.neutral	None	None	None	None	N
V/Y	0.6751	likely_pathogenic	0.6488	pathogenic	-1.586	Destabilizing	0.945	D	0.686	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.