TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30809	92650;92651;92652	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
N2AB	29168	87727;87728;87729	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
N2A	28241	84946;84947;84948	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
N2B	21744	65455;65456;65457	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
Novex-1	21869	65830;65831;65832	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
Novex-2	21936	66031;66032;66033	chr2:178549201;178549200;178549199	chr2:179413928;179413927;179413926
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-112
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.129
• 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
I/T	rs976337472	-1.598	None	N	0.356	0.101	0.43656330218	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
I/T	rs976337472	-1.598	None	N	0.356	0.101	0.43656330218	gnomAD-4.0.0	1.59121E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85785E-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
I/A	0.229	likely_benign	0.2183	benign	-1.79	Destabilizing	0.016	N	0.449	neutral	None	None	None	None	N
I/C	0.5221	ambiguous	0.5276	ambiguous	-0.863	Destabilizing	0.685	D	0.522	neutral	None	None	None	None	N
I/D	0.5636	ambiguous	0.5216	ambiguous	-0.943	Destabilizing	0.221	N	0.631	neutral	None	None	None	None	N
I/E	0.4649	ambiguous	0.4413	ambiguous	-0.899	Destabilizing	0.075	N	0.591	neutral	None	None	None	None	N
I/F	0.1481	likely_benign	0.1361	benign	-1.187	Destabilizing	0.177	N	0.433	neutral	N	0.462540012	None	None	N
I/G	0.4913	ambiguous	0.4737	ambiguous	-2.155	Highly Destabilizing	0.075	N	0.574	neutral	None	None	None	None	N
I/H	0.3994	ambiguous	0.3812	ambiguous	-1.253	Destabilizing	0.869	D	0.72	deleterious	None	None	None	None	N
I/K	0.269	likely_benign	0.2515	benign	-0.999	Destabilizing	0.075	N	0.608	neutral	None	None	None	None	N
I/L	0.1169	likely_benign	0.1158	benign	-0.841	Destabilizing	0.005	N	0.413	neutral	N	0.432550541	None	None	N
I/M	0.1117	likely_benign	0.1097	benign	-0.593	Destabilizing	0.177	N	0.441	neutral	N	0.469492776	None	None	N
I/N	0.1843	likely_benign	0.1691	benign	-0.846	Destabilizing	0.177	N	0.649	prob.neutral	N	0.471551647	None	None	N
I/P	0.3668	ambiguous	0.3408	ambiguous	-1.128	Destabilizing	0.366	N	0.651	prob.neutral	None	None	None	None	N
I/Q	0.3532	ambiguous	0.3365	benign	-0.977	Destabilizing	0.366	N	0.669	prob.neutral	None	None	None	None	N
I/R	0.2335	likely_benign	0.2271	benign	-0.452	Destabilizing	0.221	N	0.668	prob.neutral	None	None	None	None	N
I/S	0.2028	likely_benign	0.1962	benign	-1.548	Destabilizing	0.03	N	0.595	neutral	N	0.401555631	None	None	N
I/T	0.1407	likely_benign	0.1409	benign	-1.381	Destabilizing	None	N	0.356	neutral	N	0.410271114	None	None	N
I/V	0.0701	likely_benign	0.0703	benign	-1.128	Destabilizing	None	N	0.15	neutral	N	0.442900821	None	None	N
I/W	0.7512	likely_pathogenic	0.736	pathogenic	-1.269	Destabilizing	0.869	D	0.757	deleterious	None	None	None	None	N
I/Y	0.445	ambiguous	0.428	ambiguous	-1.035	Destabilizing	0.366	N	0.506	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.