TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25484	76675;76676;76677	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
N2AB	23843	71752;71753;71754	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
N2A	22916	68971;68972;68973	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
N2B	16419	49480;49481;49482	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
Novex-1	16544	49855;49856;49857	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
Novex-2	16611	50056;50057;50058	chr2:178569682;178569681;178569680	chr2:179434409;179434408;179434407
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: Fn3-73
• Domain position: 80
• Structural Position: 111
• Q(SASA): 0.2264
• 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	rs1349741599	None	0.124	N	0.501	0.253	0.552451585512	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
I/A	0.3251	likely_benign	0.3277	benign	-2.382	Highly Destabilizing	0.072	N	0.463	neutral	None	None	None	None	N
I/C	0.5705	likely_pathogenic	0.5555	ambiguous	-2.105	Highly Destabilizing	0.909	D	0.565	neutral	None	None	None	None	N
I/D	0.8179	likely_pathogenic	0.826	pathogenic	-2.416	Highly Destabilizing	0.726	D	0.697	prob.neutral	None	None	None	None	N
I/E	0.6185	likely_pathogenic	0.6222	pathogenic	-2.283	Highly Destabilizing	0.726	D	0.683	prob.neutral	None	None	None	None	N
I/F	0.1417	likely_benign	0.1577	benign	-1.554	Destabilizing	0.497	N	0.491	neutral	N	0.505397648	None	None	N
I/G	0.6535	likely_pathogenic	0.6641	pathogenic	-2.818	Highly Destabilizing	0.726	D	0.657	neutral	None	None	None	None	N
I/H	0.5692	likely_pathogenic	0.5814	pathogenic	-2.01	Highly Destabilizing	0.968	D	0.721	prob.delet.	None	None	None	None	N
I/K	0.3872	ambiguous	0.3861	ambiguous	-1.646	Destabilizing	0.726	D	0.687	prob.neutral	None	None	None	None	N
I/L	0.0882	likely_benign	0.0944	benign	-1.164	Destabilizing	0.025	N	0.329	neutral	N	0.459315855	None	None	N
I/M	0.0791	likely_benign	0.084	benign	-1.322	Destabilizing	0.497	N	0.5	neutral	N	0.49029491	None	None	N
I/N	0.3882	ambiguous	0.4212	ambiguous	-1.794	Destabilizing	0.859	D	0.714	prob.delet.	N	0.517134794	None	None	N
I/P	0.9644	likely_pathogenic	0.967	pathogenic	-1.547	Destabilizing	0.726	D	0.697	prob.neutral	None	None	None	None	N
I/Q	0.437	ambiguous	0.4512	ambiguous	-1.845	Destabilizing	0.89	D	0.721	prob.delet.	None	None	None	None	N
I/R	0.3208	likely_benign	0.3137	benign	-1.215	Destabilizing	0.726	D	0.719	prob.delet.	None	None	None	None	N
I/S	0.335	likely_benign	0.3565	ambiguous	-2.528	Highly Destabilizing	0.497	N	0.603	neutral	N	0.505571007	None	None	N
I/T	0.2009	likely_benign	0.2188	benign	-2.262	Highly Destabilizing	0.124	N	0.501	neutral	N	0.459067926	None	None	N
I/V	0.0569	likely_benign	0.0556	benign	-1.547	Destabilizing	None	N	0.164	neutral	N	0.375635679	None	None	N
I/W	0.7441	likely_pathogenic	0.7437	pathogenic	-1.721	Destabilizing	0.968	D	0.737	prob.delet.	None	None	None	None	N
I/Y	0.4883	ambiguous	0.5002	ambiguous	-1.485	Destabilizing	0.726	D	0.57	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.