TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22100	66523;66524;66525	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
N2AB	20459	61600;61601;61602	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
N2A	19532	58819;58820;58821	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
N2B	13035	39328;39329;39330	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
Novex-1	13160	39703;39704;39705	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
Novex-2	13227	39904;39905;39906	chr2:178582071;178582070;178582069	chr2:179446798;179446797;179446796
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-48
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.7002
• 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/L	None	None	None	N	0.069	0.042	0.256283259241	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

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	0.1313	likely_benign	0.1637	benign	-0.335	Destabilizing	0.001	N	0.145	neutral	N	0.502106627	None	None	N
V/C	0.604	likely_pathogenic	0.6777	pathogenic	-0.775	Destabilizing	0.944	D	0.287	neutral	None	None	None	None	N
V/D	0.3648	ambiguous	0.4134	ambiguous	-0.367	Destabilizing	0.773	D	0.355	neutral	N	0.469860923	None	None	N
V/E	0.3061	likely_benign	0.3489	ambiguous	-0.482	Destabilizing	0.69	D	0.341	neutral	None	None	None	None	N
V/F	0.1456	likely_benign	0.1828	benign	-0.724	Destabilizing	0.001	N	0.32	neutral	N	0.468824344	None	None	N
V/G	0.1517	likely_benign	0.1804	benign	-0.391	Destabilizing	0.193	N	0.332	neutral	N	0.439457871	None	None	N
V/H	0.4779	ambiguous	0.5789	pathogenic	0.01	Stabilizing	0.981	D	0.339	neutral	None	None	None	None	N
V/I	0.0664	likely_benign	0.0752	benign	-0.328	Destabilizing	0.001	N	0.201	neutral	N	0.510438109	None	None	N
V/K	0.3402	ambiguous	0.3966	ambiguous	-0.391	Destabilizing	0.69	D	0.338	neutral	None	None	None	None	N
V/L	0.109	likely_benign	0.1524	benign	-0.328	Destabilizing	None	N	0.069	neutral	N	0.440692809	None	None	N
V/M	0.1064	likely_benign	0.1373	benign	-0.592	Destabilizing	0.69	D	0.277	neutral	None	None	None	None	N
V/N	0.1913	likely_benign	0.2592	benign	-0.172	Destabilizing	0.818	D	0.349	neutral	None	None	None	None	N
V/P	0.2922	likely_benign	0.3693	ambiguous	-0.304	Destabilizing	0.818	D	0.345	neutral	None	None	None	None	N
V/Q	0.2568	likely_benign	0.3111	benign	-0.384	Destabilizing	0.818	D	0.321	neutral	None	None	None	None	N
V/R	0.3174	likely_benign	0.3539	ambiguous	0.05	Stabilizing	0.69	D	0.357	neutral	None	None	None	None	N
V/S	0.1526	likely_benign	0.1967	benign	-0.475	Destabilizing	0.241	N	0.333	neutral	None	None	None	None	N
V/T	0.1493	likely_benign	0.1843	benign	-0.502	Destabilizing	0.388	N	0.226	neutral	None	None	None	None	N
V/W	0.6736	likely_pathogenic	0.7402	pathogenic	-0.779	Destabilizing	0.981	D	0.351	neutral	None	None	None	None	N
V/Y	0.4182	ambiguous	0.4856	ambiguous	-0.507	Destabilizing	0.527	D	0.313	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.