TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21278	64057;64058;64059	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
N2AB	19637	59134;59135;59136	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
N2A	18710	56353;56354;56355	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
N2B	12213	36862;36863;36864	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
Novex-1	12338	37237;37238;37239	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
Novex-2	12405	37438;37439;37440	chr2:178587379;178587378;178587377	chr2:179452106;179452105;179452104
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: Fn3-42
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.3552
• 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/F	None	None	0.667	N	0.587	0.324	0.772501646899	gnomAD-4.0.0	2.05577E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.7009E-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
V/A	0.373	ambiguous	0.3892	ambiguous	-1.212	Destabilizing	0.001	N	0.241	neutral	N	0.495260799	None	None	N
V/C	0.779	likely_pathogenic	0.794	pathogenic	-1.532	Destabilizing	0.909	D	0.572	neutral	None	None	None	None	N
V/D	0.8432	likely_pathogenic	0.8641	pathogenic	-2.335	Highly Destabilizing	0.497	N	0.749	deleterious	N	0.498719886	None	None	N
V/E	0.7245	likely_pathogenic	0.7536	pathogenic	-2.361	Highly Destabilizing	0.567	D	0.665	neutral	None	None	None	None	N
V/F	0.389	ambiguous	0.4037	ambiguous	-1.414	Destabilizing	0.667	D	0.587	neutral	N	0.481883078	None	None	N
V/G	0.5196	ambiguous	0.54	ambiguous	-1.445	Destabilizing	0.331	N	0.659	neutral	N	0.499733844	None	None	N
V/H	0.8754	likely_pathogenic	0.8938	pathogenic	-1.083	Destabilizing	0.968	D	0.753	deleterious	None	None	None	None	N
V/I	0.0665	likely_benign	0.0694	benign	-0.675	Destabilizing	0.004	N	0.201	neutral	N	0.440308807	None	None	N
V/K	0.7006	likely_pathogenic	0.7264	pathogenic	-1.124	Destabilizing	0.567	D	0.669	neutral	None	None	None	None	N
V/L	0.3345	likely_benign	0.3669	ambiguous	-0.675	Destabilizing	0.055	N	0.364	neutral	N	0.510728897	None	None	N
V/M	0.217	likely_benign	0.2431	benign	-0.633	Destabilizing	0.726	D	0.489	neutral	None	None	None	None	N
V/N	0.6379	likely_pathogenic	0.6832	pathogenic	-1.195	Destabilizing	0.726	D	0.756	deleterious	None	None	None	None	N
V/P	0.7102	likely_pathogenic	0.7438	pathogenic	-0.824	Destabilizing	0.567	D	0.685	prob.neutral	None	None	None	None	N
V/Q	0.6977	likely_pathogenic	0.7227	pathogenic	-1.487	Destabilizing	0.726	D	0.693	prob.neutral	None	None	None	None	N
V/R	0.6713	likely_pathogenic	0.6837	pathogenic	-0.622	Destabilizing	0.567	D	0.759	deleterious	None	None	None	None	N
V/S	0.5177	ambiguous	0.5452	ambiguous	-1.528	Destabilizing	0.396	N	0.588	neutral	None	None	None	None	N
V/T	0.3018	likely_benign	0.331	benign	-1.46	Destabilizing	0.157	N	0.456	neutral	None	None	None	None	N
V/W	0.9378	likely_pathogenic	0.9477	pathogenic	-1.617	Destabilizing	0.968	D	0.738	prob.delet.	None	None	None	None	N
V/Y	0.7784	likely_pathogenic	0.7927	pathogenic	-1.225	Destabilizing	0.726	D	0.594	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.