TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33537	100834;100835;100836	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
N2AB	31896	95911;95912;95913	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
N2A	30969	93130;93131;93132	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
N2B	24472	73639;73640;73641	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
Novex-1	24597	74014;74015;74016	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
Novex-2	24664	74215;74216;74217	chr2:178536138;178536137;178536136	chr2:179400865;179400864;179400863
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-158
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.4615
• 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
I/F	rs1184341890	None	0.523	N	0.235	0.176	0.436025050644	gnomAD-4.0.0	4.77468E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57604E-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	0.1353	likely_benign	0.1151	benign	-0.509	Destabilizing	0.397	N	0.284	neutral	None	None	None	None	I
I/C	0.5416	ambiguous	0.4601	ambiguous	-0.71	Destabilizing	0.988	D	0.309	neutral	None	None	None	None	I
I/D	0.4193	ambiguous	0.3789	ambiguous	-0.272	Destabilizing	0.005	N	0.195	neutral	None	None	None	None	I
I/E	0.3032	likely_benign	0.266	benign	-0.347	Destabilizing	0.015	N	0.193	neutral	None	None	None	None	I
I/F	0.1332	likely_benign	0.122	benign	-0.552	Destabilizing	0.523	D	0.235	neutral	N	0.505544869	None	None	I
I/G	0.3909	ambiguous	0.3432	ambiguous	-0.651	Destabilizing	0.754	D	0.385	neutral	None	None	None	None	I
I/H	0.2795	likely_benign	0.255	benign	0.07	Stabilizing	0.915	D	0.344	neutral	None	None	None	None	I
I/K	0.1882	likely_benign	0.189	benign	-0.358	Destabilizing	0.022	N	0.405	neutral	None	None	None	None	I
I/L	0.0796	likely_benign	0.0772	benign	-0.247	Destabilizing	None	N	0.113	neutral	N	0.444688411	None	None	I
I/M	0.0768	likely_benign	0.074	benign	-0.55	Destabilizing	0.013	N	0.209	neutral	D	0.526824218	None	None	I
I/N	0.1388	likely_benign	0.1203	benign	-0.23	Destabilizing	0.734	D	0.47	neutral	N	0.476008609	None	None	I
I/P	0.3817	ambiguous	0.3293	benign	-0.305	Destabilizing	0.958	D	0.459	neutral	None	None	None	None	I
I/Q	0.1958	likely_benign	0.1738	benign	-0.399	Destabilizing	0.056	N	0.229	neutral	None	None	None	None	I
I/R	0.1626	likely_benign	0.1721	benign	0.124	Stabilizing	0.593	D	0.451	neutral	None	None	None	None	I
I/S	0.1391	likely_benign	0.1226	benign	-0.627	Destabilizing	0.532	D	0.318	neutral	N	0.458577641	None	None	I
I/T	0.0838	likely_benign	0.077	benign	-0.594	Destabilizing	0.255	N	0.374	neutral	N	0.455596051	None	None	I
I/V	0.0689	likely_benign	0.068	benign	-0.305	Destabilizing	0.01	N	0.191	neutral	N	0.475568679	None	None	I
I/W	0.6528	likely_pathogenic	0.6181	pathogenic	-0.588	Destabilizing	0.998	D	0.33	neutral	None	None	None	None	I
I/Y	0.4345	ambiguous	0.4067	ambiguous	-0.343	Destabilizing	0.257	N	0.384	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.