TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29956	90091;90092;90093	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
N2AB	28315	85168;85169;85170	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
N2A	27388	82387;82388;82389	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
N2B	20891	62896;62897;62898	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
Novex-1	21016	63271;63272;63273	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
Novex-2	21083	63472;63473;63474	chr2:178553034;178553033;178553032	chr2:179417761;179417760;179417759
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-106
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.4392
• Predicted PPI site: I

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
P/L	None	None	0.549	N	0.518	0.503	0.659023422603	gnomAD-4.0.0	2.05542E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79899E-06	0	1.65717E-05
P/S	rs773071868	-1.855	0.007	N	0.243	0.223	0.27132560031	gnomAD-2.1.1	8.1E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
P/S	rs773071868	-1.855	0.007	N	0.243	0.223	0.27132560031	gnomAD-4.0.0	4.11062E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.6985E-06	3.47858E-05	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
P/A	0.0765	likely_benign	0.076	benign	-1.716	Destabilizing	0.007	N	0.247	neutral	N	0.485102521	None	None	I
P/C	0.5377	ambiguous	0.4902	ambiguous	-1.058	Destabilizing	0.992	D	0.593	neutral	None	None	None	None	I
P/D	0.6684	likely_pathogenic	0.6538	pathogenic	-1.779	Destabilizing	0.617	D	0.481	neutral	None	None	None	None	I
P/E	0.3535	ambiguous	0.3701	ambiguous	-1.728	Destabilizing	0.617	D	0.441	neutral	None	None	None	None	I
P/F	0.5712	likely_pathogenic	0.5385	ambiguous	-1.266	Destabilizing	0.92	D	0.602	neutral	None	None	None	None	I
P/G	0.4561	ambiguous	0.4399	ambiguous	-2.082	Highly Destabilizing	0.25	N	0.465	neutral	None	None	None	None	I
P/H	0.2655	likely_benign	0.2628	benign	-1.59	Destabilizing	0.97	D	0.569	neutral	N	0.520297315	None	None	I
P/I	0.2627	likely_benign	0.2527	benign	-0.778	Destabilizing	0.92	D	0.61	neutral	None	None	None	None	I
P/K	0.3222	likely_benign	0.3256	benign	-1.484	Destabilizing	0.447	N	0.452	neutral	None	None	None	None	I
P/L	0.1257	likely_benign	0.1197	benign	-0.778	Destabilizing	0.549	D	0.518	neutral	N	0.497900646	None	None	I
P/M	0.2605	likely_benign	0.2526	benign	-0.567	Destabilizing	0.992	D	0.571	neutral	None	None	None	None	I
P/N	0.4454	ambiguous	0.4027	ambiguous	-1.334	Destabilizing	0.739	D	0.585	neutral	None	None	None	None	I
P/Q	0.1763	likely_benign	0.1769	benign	-1.447	Destabilizing	0.85	D	0.573	neutral	None	None	None	None	I
P/R	0.2542	likely_benign	0.2544	benign	-0.961	Destabilizing	0.81	D	0.599	neutral	N	0.493038801	None	None	I
P/S	0.1488	likely_benign	0.1388	benign	-1.842	Destabilizing	0.007	N	0.243	neutral	N	0.484062352	None	None	I
P/T	0.1185	likely_benign	0.1155	benign	-1.673	Destabilizing	0.379	N	0.459	neutral	N	0.494849226	None	None	I
P/V	0.1826	likely_benign	0.1766	benign	-1.058	Destabilizing	0.617	D	0.499	neutral	None	None	None	None	I
P/W	0.8296	likely_pathogenic	0.8207	pathogenic	-1.518	Destabilizing	0.992	D	0.65	neutral	None	None	None	None	I
P/Y	0.5653	likely_pathogenic	0.5411	ambiguous	-1.224	Destabilizing	0.972	D	0.601	neutral	None	None	None	None	I

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.