TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17932	54019;54020;54021	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
N2AB	16291	49096;49097;49098	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
N2A	15364	46315;46316;46317	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
N2B	8867	26824;26825;26826	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
Novex-1	8992	27199;27200;27201	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
Novex-2	9059	27400;27401;27402	chr2:178605501;178605500;178605499	chr2:179470228;179470227;179470226
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-18
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3707
• 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
M/I	rs1195735577	None	0.993	N	0.397	0.359	0.472504041403	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
M/T	None	None	0.979	N	0.383	0.263	0.7014751448	gnomAD-4.0.0	6.8479E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00101E-07	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
M/A	0.8664	likely_pathogenic	0.836	pathogenic	-2.672	Highly Destabilizing	0.927	D	0.368	neutral	None	None	None	None	N
M/C	0.9206	likely_pathogenic	0.8894	pathogenic	-1.743	Destabilizing	1.0	D	0.492	neutral	None	None	None	None	N
M/D	0.9525	likely_pathogenic	0.9521	pathogenic	-1.64	Destabilizing	0.995	D	0.538	neutral	None	None	None	None	N
M/E	0.8709	likely_pathogenic	0.821	pathogenic	-1.519	Destabilizing	0.969	D	0.461	neutral	None	None	None	None	N
M/F	0.653	likely_pathogenic	0.6305	pathogenic	-1.265	Destabilizing	0.999	D	0.462	neutral	None	None	None	None	N
M/G	0.9311	likely_pathogenic	0.919	pathogenic	-3.068	Highly Destabilizing	0.984	D	0.517	neutral	None	None	None	None	N
M/H	0.8716	likely_pathogenic	0.8354	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.541	neutral	None	None	None	None	N
M/I	0.8312	likely_pathogenic	0.7932	pathogenic	-1.568	Destabilizing	0.993	D	0.397	neutral	N	0.454699469	None	None	N
M/K	0.7542	likely_pathogenic	0.7042	pathogenic	-1.505	Destabilizing	0.238	N	0.233	neutral	N	0.421200184	None	None	N
M/L	0.31	likely_benign	0.3174	benign	-1.568	Destabilizing	0.895	D	0.217	neutral	N	0.447637424	None	None	N
M/N	0.7841	likely_pathogenic	0.7429	pathogenic	-1.496	Destabilizing	0.995	D	0.523	neutral	None	None	None	None	N
M/P	0.9403	likely_pathogenic	0.9266	pathogenic	-1.916	Destabilizing	0.999	D	0.527	neutral	None	None	None	None	N
M/Q	0.625	likely_pathogenic	0.5511	ambiguous	-1.438	Destabilizing	0.969	D	0.437	neutral	None	None	None	None	N
M/R	0.7653	likely_pathogenic	0.7257	pathogenic	-1.113	Destabilizing	0.921	D	0.429	neutral	N	0.431033176	None	None	N
M/S	0.8367	likely_pathogenic	0.801	pathogenic	-2.137	Highly Destabilizing	0.969	D	0.389	neutral	None	None	None	None	N
M/T	0.7558	likely_pathogenic	0.6889	pathogenic	-1.909	Destabilizing	0.979	D	0.383	neutral	N	0.409772469	None	None	N
M/V	0.3933	ambiguous	0.3338	benign	-1.916	Destabilizing	0.951	D	0.418	neutral	N	0.427051508	None	None	N
M/W	0.8801	likely_pathogenic	0.8777	pathogenic	-1.32	Destabilizing	1.0	D	0.511	neutral	None	None	None	None	N
M/Y	0.8301	likely_pathogenic	0.8023	pathogenic	-1.443	Destabilizing	0.999	D	0.508	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.