TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28510	85753;85754;85755	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
N2AB	26869	80830;80831;80832	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
N2A	25942	78049;78050;78051	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
N2B	19445	58558;58559;58560	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
Novex-1	19570	58933;58934;58935	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
Novex-2	19637	59134;59135;59136	chr2:178560604;178560603;178560602	chr2:179425331;179425330;179425329
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-95
• Domain position: 61
• Structural Position: 91
• Q(SASA): 0.1672
• 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
C/Y	None	None	1.0	N	0.855	0.454	0.652629836549	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	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
C/A	0.5121	ambiguous	0.4877	ambiguous	-1.596	Destabilizing	0.998	D	0.604	neutral	None	None	None	None	N
C/D	0.9183	likely_pathogenic	0.9008	pathogenic	0.17	Stabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
C/E	0.9116	likely_pathogenic	0.8953	pathogenic	0.307	Stabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
C/F	0.1836	likely_benign	0.1806	benign	-1.034	Destabilizing	1.0	D	0.851	deleterious	N	0.443711684	None	None	N
C/G	0.3542	ambiguous	0.322	benign	-1.915	Destabilizing	1.0	D	0.8	deleterious	N	0.496296668	None	None	N
C/H	0.5648	likely_pathogenic	0.5534	ambiguous	-1.807	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
C/I	0.4774	ambiguous	0.439	ambiguous	-0.769	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
C/K	0.8231	likely_pathogenic	0.8023	pathogenic	-0.436	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
C/L	0.3849	ambiguous	0.3668	ambiguous	-0.769	Destabilizing	0.999	D	0.639	neutral	None	None	None	None	N
C/M	0.6333	likely_pathogenic	0.6239	pathogenic	0.015	Stabilizing	1.0	D	0.816	deleterious	None	None	None	None	N
C/N	0.7766	likely_pathogenic	0.7623	pathogenic	-0.666	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
C/P	0.9852	likely_pathogenic	0.9819	pathogenic	-1.019	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
C/Q	0.7246	likely_pathogenic	0.6927	pathogenic	-0.428	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
C/R	0.4841	ambiguous	0.4447	ambiguous	-0.506	Destabilizing	1.0	D	0.877	deleterious	N	0.507817557	None	None	N
C/S	0.4731	ambiguous	0.4485	ambiguous	-1.228	Destabilizing	1.0	D	0.755	deleterious	N	0.484686873	None	None	N
C/T	0.5869	likely_pathogenic	0.5489	ambiguous	-0.88	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
C/V	0.4233	ambiguous	0.3907	ambiguous	-1.019	Destabilizing	0.999	D	0.665	neutral	None	None	None	None	N
C/W	0.5196	ambiguous	0.4836	ambiguous	-1.024	Destabilizing	1.0	D	0.84	deleterious	N	0.475723651	None	None	N
C/Y	0.266	likely_benign	0.2657	benign	-0.969	Destabilizing	1.0	D	0.855	deleterious	N	0.412289912	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.