TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2696	8311;8312;8313	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
N2AB	2696	8311;8312;8313	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
N2A	2696	8311;8312;8313	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
N2B	2650	8173;8174;8175	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
Novex-1	2650	8173;8174;8175	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
Novex-2	2650	8173;8174;8175	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966
Novex-3	2696	8311;8312;8313	chr2:178771241;178771240;178771239	chr2:179635968;179635967;179635966

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-16
• Domain position: 76
• Structural Position: 162
• Q(SASA): 0.1369
• 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
S/P	None	None	1.0	D	0.803	0.623	0.510700632011	gnomAD-4.0.0	1.59067E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
S/A	0.1346	likely_benign	0.1408	benign	-0.319	Destabilizing	0.997	D	0.514	neutral	N	0.510286171	None	None	N
S/C	0.3601	ambiguous	0.3107	benign	-0.362	Destabilizing	1.0	D	0.784	deleterious	D	0.589874313	None	None	N
S/D	0.761	likely_pathogenic	0.7413	pathogenic	0.157	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
S/E	0.8129	likely_pathogenic	0.8119	pathogenic	0.097	Stabilizing	0.999	D	0.665	neutral	None	None	None	None	N
S/F	0.7005	likely_pathogenic	0.7089	pathogenic	-0.727	Destabilizing	1.0	D	0.827	deleterious	N	0.518246721	None	None	N
S/G	0.2372	likely_benign	0.2423	benign	-0.489	Destabilizing	0.999	D	0.561	neutral	None	None	None	None	N
S/H	0.7857	likely_pathogenic	0.7668	pathogenic	-0.969	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
S/I	0.6188	likely_pathogenic	0.6255	pathogenic	0.002	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/K	0.9461	likely_pathogenic	0.9439	pathogenic	-0.572	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
S/L	0.3169	likely_benign	0.3305	benign	0.002	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
S/M	0.5631	ambiguous	0.5697	pathogenic	0.058	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
S/N	0.4738	ambiguous	0.4531	ambiguous	-0.375	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
S/P	0.9518	likely_pathogenic	0.9441	pathogenic	-0.073	Destabilizing	1.0	D	0.803	deleterious	D	0.572421736	None	None	N
S/Q	0.813	likely_pathogenic	0.8087	pathogenic	-0.543	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
S/R	0.9099	likely_pathogenic	0.9065	pathogenic	-0.417	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
S/T	0.1848	likely_benign	0.1966	benign	-0.423	Destabilizing	0.999	D	0.548	neutral	N	0.5194734	None	None	N
S/V	0.5131	ambiguous	0.5146	ambiguous	-0.073	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
S/W	0.7904	likely_pathogenic	0.7842	pathogenic	-0.76	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
S/Y	0.5872	likely_pathogenic	0.5752	pathogenic	-0.471	Destabilizing	1.0	D	0.829	deleterious	D	0.54613706	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.