TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9613	29062;29063;29064	chr2:178707730;178707729;178707728	chr2:179572457;179572456;179572455
N2AB	9296	28111;28112;28113	chr2:178707730;178707729;178707728	chr2:179572457;179572456;179572455
N2A	8369	25330;25331;25332	chr2:178707730;178707729;178707728	chr2:179572457;179572456;179572455
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-82
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1619
• 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/I	rs749649816	-0.581	0.543	None	0.263	0.218	0.389439708392	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.86E-06	0
V/I	rs749649816	-0.581	0.543	None	0.263	0.218	0.389439708392	gnomAD-4.0.0	1.59106E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85791E-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	0.6472	likely_pathogenic	0.5829	pathogenic	-2.13	Highly Destabilizing	0.989	D	0.66	neutral	None	None	None	None	N
V/C	0.9238	likely_pathogenic	0.9184	pathogenic	-1.659	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
V/D	0.9963	likely_pathogenic	0.9946	pathogenic	-3.087	Highly Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/E	0.9827	likely_pathogenic	0.9781	pathogenic	-2.843	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
V/F	0.6652	likely_pathogenic	0.5502	ambiguous	-1.206	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
V/G	0.8465	likely_pathogenic	0.8177	pathogenic	-2.672	Highly Destabilizing	0.998	D	0.837	deleterious	None	None	None	None	N
V/H	0.992	likely_pathogenic	0.988	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/I	0.1153	likely_benign	0.1037	benign	-0.587	Destabilizing	0.543	D	0.263	neutral	None	None	None	None	N
V/K	0.9807	likely_pathogenic	0.9773	pathogenic	-1.714	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
V/L	0.4903	ambiguous	0.4545	ambiguous	-0.587	Destabilizing	0.948	D	0.457	neutral	None	None	None	None	N
V/M	0.4826	ambiguous	0.4106	ambiguous	-0.713	Destabilizing	0.96	D	0.519	neutral	None	None	None	None	N
V/N	0.9859	likely_pathogenic	0.98	pathogenic	-2.155	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
V/P	0.9871	likely_pathogenic	0.9849	pathogenic	-1.079	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
V/Q	0.9699	likely_pathogenic	0.9622	pathogenic	-1.935	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/R	0.9606	likely_pathogenic	0.9548	pathogenic	-1.635	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/S	0.8899	likely_pathogenic	0.8435	pathogenic	-2.688	Highly Destabilizing	0.999	D	0.807	deleterious	None	None	None	None	N
V/T	0.7617	likely_pathogenic	0.7095	pathogenic	-2.309	Highly Destabilizing	0.996	D	0.682	prob.neutral	None	None	None	None	N
V/W	0.9927	likely_pathogenic	0.9878	pathogenic	-1.857	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
V/Y	0.966	likely_pathogenic	0.9508	pathogenic	-1.485	Destabilizing	1.0	D	0.772	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.