TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32359	97300;97301;97302	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
N2AB	30718	92377;92378;92379	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
N2A	29791	89596;89597;89598	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
N2B	23294	70105;70106;70107	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
Novex-1	23419	70480;70481;70482	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
Novex-2	23486	70681;70682;70683	chr2:178542779;178542778;178542777	chr2:179407506;179407505;179407504
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-154
• Domain position: 53
• Structural Position: 131
• Q(SASA): 0.5865
• 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
T/I	rs759803579	0.048	0.175	N	0.392	0.043	0.112648838833	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs759803579	0.048	0.175	N	0.392	0.043	0.112648838833	gnomAD-4.0.0	2.05261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99465E-07	0	3.31323E-05

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
T/A	0.0623	likely_benign	0.0573	benign	-0.343	Destabilizing	None	N	0.117	neutral	N	0.412340266	None	None	N
T/C	0.2985	likely_benign	0.2564	benign	-0.389	Destabilizing	0.667	D	0.341	neutral	None	None	None	None	N
T/D	0.2268	likely_benign	0.1854	benign	0.207	Stabilizing	0.055	N	0.293	neutral	None	None	None	None	N
T/E	0.1958	likely_benign	0.157	benign	0.16	Stabilizing	0.055	N	0.295	neutral	None	None	None	None	N
T/F	0.2253	likely_benign	0.1764	benign	-0.659	Destabilizing	0.667	D	0.421	neutral	None	None	None	None	N
T/G	0.1225	likely_benign	0.1062	benign	-0.515	Destabilizing	None	N	0.153	neutral	None	None	None	None	N
T/H	0.1749	likely_benign	0.1426	benign	-0.736	Destabilizing	0.667	D	0.368	neutral	None	None	None	None	N
T/I	0.1577	likely_benign	0.1297	benign	-0.003	Destabilizing	0.175	N	0.392	neutral	N	0.443279249	None	None	N
T/K	0.1399	likely_benign	0.1195	benign	-0.488	Destabilizing	0.055	N	0.301	neutral	None	None	None	None	N
T/L	0.0815	likely_benign	0.0719	benign	-0.003	Destabilizing	0.055	N	0.298	neutral	None	None	None	None	N
T/M	0.0892	likely_benign	0.0825	benign	-0.051	Destabilizing	0.667	D	0.342	neutral	None	None	None	None	N
T/N	0.0781	likely_benign	0.0752	benign	-0.32	Destabilizing	None	N	0.164	neutral	N	0.397909532	None	None	N
T/P	0.0622	likely_benign	0.0577	benign	-0.085	Destabilizing	0.301	N	0.352	neutral	N	0.398429607	None	None	N
T/Q	0.1368	likely_benign	0.116	benign	-0.475	Destabilizing	0.22	N	0.394	neutral	None	None	None	None	N
T/R	0.114	likely_benign	0.0978	benign	-0.241	Destabilizing	0.22	N	0.331	neutral	None	None	None	None	N
T/S	0.0777	likely_benign	0.0714	benign	-0.534	Destabilizing	None	N	0.109	neutral	N	0.400352404	None	None	N
T/V	0.1241	likely_benign	0.1039	benign	-0.085	Destabilizing	0.055	N	0.16	neutral	None	None	None	None	N
T/W	0.4266	ambiguous	0.3669	ambiguous	-0.682	Destabilizing	0.958	D	0.361	neutral	None	None	None	None	N
T/Y	0.2098	likely_benign	0.1741	benign	-0.407	Destabilizing	0.667	D	0.385	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.