TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28739	86440;86441;86442	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
N2AB	27098	81517;81518;81519	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
N2A	26171	78736;78737;78738	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
N2B	19674	59245;59246;59247	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
Novex-1	19799	59620;59621;59622	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
Novex-2	19866	59821;59822;59823	chr2:178559917;178559916;178559915	chr2:179424644;179424643;179424642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-97
• Domain position: 89
• Structural Position: 123
• Q(SASA): 0.2602
• 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
S/R	rs1468503993	-0.636	0.047	N	0.644	0.09	0.132336055621	gnomAD-2.1.1	3.18E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-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
S/A	0.0667	likely_benign	0.0728	benign	-0.913	Destabilizing	0.012	N	0.385	neutral	None	None	None	None	N
S/C	0.0756	likely_benign	0.0817	benign	-0.604	Destabilizing	0.681	D	0.597	neutral	N	0.493465714	None	None	N
S/D	0.394	ambiguous	0.3641	ambiguous	-0.633	Destabilizing	0.026	N	0.388	neutral	None	None	None	None	N
S/E	0.495	ambiguous	0.4805	ambiguous	-0.597	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
S/F	0.1534	likely_benign	0.1788	benign	-0.96	Destabilizing	0.314	N	0.74	deleterious	None	None	None	None	N
S/G	0.0865	likely_benign	0.0929	benign	-1.201	Destabilizing	0.02	N	0.431	neutral	N	0.51807337	None	None	N
S/H	0.341	ambiguous	0.3395	benign	-1.624	Destabilizing	0.314	N	0.611	neutral	None	None	None	None	N
S/I	0.0788	likely_benign	0.0835	benign	-0.236	Destabilizing	None	N	0.555	neutral	N	0.43786036	None	None	N
S/K	0.6387	likely_pathogenic	0.6253	pathogenic	-0.788	Destabilizing	0.001	N	0.233	neutral	None	None	None	None	N
S/L	0.0792	likely_benign	0.0844	benign	-0.236	Destabilizing	0.004	N	0.643	neutral	None	None	None	None	N
S/M	0.1494	likely_benign	0.1633	benign	0.07	Stabilizing	0.314	N	0.628	neutral	None	None	None	None	N
S/N	0.1308	likely_benign	0.1376	benign	-0.861	Destabilizing	None	N	0.19	neutral	N	0.463662882	None	None	N
S/P	0.1385	likely_benign	0.1399	benign	-0.428	Destabilizing	0.209	N	0.668	prob.neutral	None	None	None	None	N
S/Q	0.468	ambiguous	0.4583	ambiguous	-0.97	Destabilizing	0.116	N	0.511	neutral	None	None	None	None	N
S/R	0.5641	likely_pathogenic	0.5576	ambiguous	-0.726	Destabilizing	0.047	N	0.644	neutral	N	0.498871534	None	None	N
S/T	0.0671	likely_benign	0.0742	benign	-0.826	Destabilizing	None	N	0.233	neutral	N	0.431569106	None	None	N
S/V	0.0916	likely_benign	0.0961	benign	-0.428	Destabilizing	None	N	0.564	neutral	None	None	None	None	N
S/W	0.3472	ambiguous	0.3782	ambiguous	-0.948	Destabilizing	0.914	D	0.733	deleterious	None	None	None	None	N
S/Y	0.1702	likely_benign	0.1875	benign	-0.681	Destabilizing	0.482	N	0.753	deleterious	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.