TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26297	79114;79115;79116	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
N2AB	24656	74191;74192;74193	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
N2A	23729	71410;71411;71412	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
N2B	17232	51919;51920;51921	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
Novex-1	17357	52294;52295;52296	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
Novex-2	17424	52495;52496;52497	chr2:178567243;178567242;178567241	chr2:179431970;179431969;179431968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-79
• Domain position: 12
• Structural Position: 13
• Q(SASA): 0.6314
• 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
T/A	None	None	0.003	N	0.093	0.136	0.112648838833	gnomAD-4.0.0	1.60862E-06	None	None	None	None	N	None	0	0	None	0	2.7787E-05	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
T/A	0.0851	likely_benign	0.0894	benign	-0.449	Destabilizing	0.003	N	0.093	neutral	N	0.510728897	None	None	N
T/C	0.3354	likely_benign	0.3371	benign	-0.254	Destabilizing	0.987	D	0.43	neutral	None	None	None	None	N
T/D	0.3837	ambiguous	0.3851	ambiguous	0.233	Stabilizing	0.742	D	0.433	neutral	None	None	None	None	N
T/E	0.3571	ambiguous	0.3753	ambiguous	0.157	Stabilizing	0.742	D	0.37	neutral	None	None	None	None	N
T/F	0.1991	likely_benign	0.2051	benign	-0.952	Destabilizing	0.953	D	0.493	neutral	None	None	None	None	N
T/G	0.1912	likely_benign	0.1948	benign	-0.578	Destabilizing	0.373	N	0.404	neutral	None	None	None	None	N
T/H	0.2382	likely_benign	0.2306	benign	-0.903	Destabilizing	0.996	D	0.469	neutral	None	None	None	None	N
T/I	0.1827	likely_benign	0.1994	benign	-0.228	Destabilizing	0.884	D	0.434	neutral	N	0.469611266	None	None	N
T/K	0.2562	likely_benign	0.258	benign	-0.343	Destabilizing	0.742	D	0.375	neutral	None	None	None	None	N
T/L	0.1027	likely_benign	0.1058	benign	-0.228	Destabilizing	0.59	D	0.381	neutral	None	None	None	None	N
T/M	0.0911	likely_benign	0.0924	benign	0.027	Stabilizing	0.984	D	0.43	neutral	None	None	None	None	N
T/N	0.1202	likely_benign	0.1164	benign	-0.126	Destabilizing	0.684	D	0.402	neutral	N	0.479348183	None	None	N
T/P	0.5695	likely_pathogenic	0.5949	pathogenic	-0.273	Destabilizing	0.939	D	0.439	neutral	N	0.488502442	None	None	N
T/Q	0.2603	likely_benign	0.2593	benign	-0.369	Destabilizing	0.953	D	0.451	neutral	None	None	None	None	N
T/R	0.2277	likely_benign	0.2289	benign	-0.083	Destabilizing	0.91	D	0.448	neutral	None	None	None	None	N
T/S	0.0811	likely_benign	0.082	benign	-0.365	Destabilizing	0.012	N	0.114	neutral	N	0.409927185	None	None	N
T/V	0.1378	likely_benign	0.1464	benign	-0.273	Destabilizing	0.59	D	0.379	neutral	None	None	None	None	N
T/W	0.5013	ambiguous	0.4926	ambiguous	-0.933	Destabilizing	0.996	D	0.587	neutral	None	None	None	None	N
T/Y	0.2604	likely_benign	0.2613	benign	-0.654	Destabilizing	0.984	D	0.487	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.