TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25258	75997;75998;75999	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
N2AB	23617	71074;71075;71076	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
N2A	22690	68293;68294;68295	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
N2B	16193	48802;48803;48804	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
Novex-1	16318	49177;49178;49179	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
Novex-2	16385	49378;49379;49380	chr2:178570360;178570359;178570358	chr2:179435087;179435086;179435085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-71
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.6739
• 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
N/S	rs768945739	0.074	None	N	0.115	0.134	0.112648838833	gnomAD-2.1.1	3.24E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	7.17E-05	0
N/S	rs768945739	0.074	None	N	0.115	0.134	0.112648838833	gnomAD-4.0.0	1.0951E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.34937E-05	1.15953E-05	0
N/T	rs768945739	0.142	0.062	N	0.301	0.091	0.176091768786	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	1.14758E-04	0	None	0	0	None	0	None	0	0	0
N/T	rs768945739	0.142	0.062	N	0.301	0.091	0.176091768786	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
N/T	rs768945739	0.142	0.062	N	0.301	0.091	0.176091768786	gnomAD-4.0.0	6.57479E-06	None	None	None	None	I	None	2.41301E-05	0	None	0	0	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
N/A	0.1373	likely_benign	0.1586	benign	-0.356	Destabilizing	0.035	N	0.316	neutral	None	None	None	None	I
N/C	0.1884	likely_benign	0.248	benign	0.418	Stabilizing	0.824	D	0.326	neutral	None	None	None	None	I
N/D	0.113	likely_benign	0.1223	benign	-0.158	Destabilizing	None	N	0.106	neutral	N	0.385895532	None	None	I
N/E	0.2628	likely_benign	0.2937	benign	-0.187	Destabilizing	0.035	N	0.31	neutral	None	None	None	None	I
N/F	0.4626	ambiguous	0.5338	ambiguous	-0.638	Destabilizing	0.555	D	0.335	neutral	None	None	None	None	I
N/G	0.1959	likely_benign	0.2175	benign	-0.552	Destabilizing	0.035	N	0.311	neutral	None	None	None	None	I
N/H	0.0871	likely_benign	0.0942	benign	-0.601	Destabilizing	0.484	N	0.39	neutral	N	0.433766836	None	None	I
N/I	0.2182	likely_benign	0.2654	benign	0.078	Stabilizing	0.317	N	0.369	neutral	N	0.479096481	None	None	I
N/K	0.1849	likely_benign	0.2037	benign	-0.001	Destabilizing	0.001	N	0.107	neutral	N	0.424048488	None	None	I
N/L	0.2225	likely_benign	0.2637	benign	0.078	Stabilizing	0.149	N	0.369	neutral	None	None	None	None	I
N/M	0.268	likely_benign	0.3177	benign	0.533	Stabilizing	0.935	D	0.32	neutral	None	None	None	None	I
N/P	0.6596	likely_pathogenic	0.6734	pathogenic	-0.039	Destabilizing	0.38	N	0.354	neutral	None	None	None	None	I
N/Q	0.2164	likely_benign	0.2444	benign	-0.458	Destabilizing	0.149	N	0.361	neutral	None	None	None	None	I
N/R	0.2249	likely_benign	0.2466	benign	0.087	Stabilizing	0.081	N	0.293	neutral	None	None	None	None	I
N/S	0.0695	likely_benign	0.0735	benign	-0.187	Destabilizing	None	N	0.115	neutral	N	0.419333315	None	None	I
N/T	0.0985	likely_benign	0.1095	benign	-0.078	Destabilizing	0.062	N	0.301	neutral	N	0.430763817	None	None	I
N/V	0.1739	likely_benign	0.2122	benign	-0.039	Destabilizing	0.149	N	0.367	neutral	None	None	None	None	I
N/W	0.7357	likely_pathogenic	0.7808	pathogenic	-0.596	Destabilizing	0.935	D	0.491	neutral	None	None	None	None	I
N/Y	0.1706	likely_benign	0.1961	benign	-0.351	Destabilizing	0.484	N	0.335	neutral	N	0.493641859	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.