TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27622	83089;83090;83091	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
N2AB	25981	78166;78167;78168	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
N2A	25054	75385;75386;75387	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
N2B	18557	55894;55895;55896	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
Novex-1	18682	56269;56270;56271	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
Novex-2	18749	56470;56471;56472	chr2:178563268;178563267;178563266	chr2:179427995;179427994;179427993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-89
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.3942
• 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
P/T	rs769189431	-1.124	0.988	N	0.713	0.366	0.376393476264	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.24018E-04	2.83E-05	None	0	0	None	0	None	0	0	0
P/T	rs769189431	-1.124	0.988	N	0.713	0.366	0.376393476264	gnomAD-3.1.2	6.58E-05	None	None	None	None	N	None	2.41383E-04	0	0	0	0	None	0	0	0	0	0
P/T	rs769189431	-1.124	0.988	N	0.713	0.366	0.376393476264	gnomAD-4.0.0	9.91618E-06	None	None	None	None	N	None	1.86936E-04	3.33511E-05	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
P/A	0.1242	likely_benign	0.1338	benign	-0.587	Destabilizing	0.958	D	0.589	neutral	N	0.496794021	None	None	N
P/C	0.6877	likely_pathogenic	0.7081	pathogenic	-0.676	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
P/D	0.6601	likely_pathogenic	0.6745	pathogenic	-0.174	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
P/E	0.4447	ambiguous	0.4566	ambiguous	-0.264	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
P/F	0.5968	likely_pathogenic	0.6291	pathogenic	-0.687	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
P/G	0.4562	ambiguous	0.4741	ambiguous	-0.752	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
P/H	0.3366	likely_benign	0.3521	ambiguous	-0.258	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
P/I	0.4068	ambiguous	0.4353	ambiguous	-0.291	Destabilizing	0.982	D	0.741	deleterious	None	None	None	None	N
P/K	0.4572	ambiguous	0.4685	ambiguous	-0.489	Destabilizing	0.995	D	0.754	deleterious	None	None	None	None	N
P/L	0.1427	likely_benign	0.1539	benign	-0.291	Destabilizing	0.142	N	0.511	neutral	N	0.492521565	None	None	N
P/M	0.3803	ambiguous	0.4123	ambiguous	-0.378	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
P/N	0.5088	ambiguous	0.5421	ambiguous	-0.244	Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
P/Q	0.2729	likely_benign	0.2824	benign	-0.445	Destabilizing	0.998	D	0.785	deleterious	N	0.519710953	None	None	N
P/R	0.3629	ambiguous	0.3592	ambiguous	0.003	Stabilizing	0.994	D	0.779	deleterious	N	0.518670803	None	None	N
P/S	0.1839	likely_benign	0.1979	benign	-0.668	Destabilizing	0.994	D	0.751	deleterious	N	0.46935949	None	None	N
P/T	0.1813	likely_benign	0.1892	benign	-0.647	Destabilizing	0.988	D	0.713	prob.delet.	N	0.46533775	None	None	N
P/V	0.2856	likely_benign	0.3039	benign	-0.354	Destabilizing	0.982	D	0.698	prob.neutral	None	None	None	None	N
P/W	0.8182	likely_pathogenic	0.8143	pathogenic	-0.771	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/Y	0.5952	likely_pathogenic	0.6153	pathogenic	-0.476	Destabilizing	0.999	D	0.787	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.