TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5591	16996;16997;16998	chr2:178732198;178732197;178732196	chr2:179596925;179596924;179596923
N2AB	5274	16045;16046;16047	chr2:178732198;178732197;178732196	chr2:179596925;179596924;179596923
N2A	4347	13264;13265;13266	chr2:178732198;178732197;178732196	chr2:179596925;179596924;179596923
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-39
• Domain position: 49
• Structural Position: 122
• Q(SASA): 0.285
• 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
R/I	rs750316973	-0.159	0.001	N	0.243	0.179	0.222439326576	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.22643E-04	None	0	None	0	0	0
R/I	rs750316973	-0.159	0.001	N	0.243	0.179	0.222439326576	gnomAD-4.0.0	1.0263E-05	None	None	None	None	N	None	0	0	None	0	1.00776E-04	None	0	0	9.89408E-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
R/A	0.1393	likely_benign	0.1544	benign	-0.814	Destabilizing	0.007	N	0.189	neutral	None	None	None	None	N
R/C	0.1733	likely_benign	0.1749	benign	-0.744	Destabilizing	0.356	N	0.319	neutral	None	None	None	None	N
R/D	0.3107	likely_benign	0.3414	ambiguous	-0.146	Destabilizing	0.031	N	0.334	neutral	None	None	None	None	N
R/E	0.1379	likely_benign	0.1544	benign	-0.069	Destabilizing	0.007	N	0.167	neutral	None	None	None	None	N
R/F	0.2725	likely_benign	0.2924	benign	-0.954	Destabilizing	0.356	N	0.393	neutral	None	None	None	None	N
R/G	0.1169	likely_benign	0.1297	benign	-1.059	Destabilizing	0.024	N	0.331	neutral	D	0.534310338	None	None	N
R/H	0.0912	likely_benign	0.0864	benign	-1.313	Destabilizing	0.356	N	0.249	neutral	None	None	None	None	N
R/I	0.1082	likely_benign	0.1116	benign	-0.175	Destabilizing	0.001	N	0.243	neutral	N	0.485518653	None	None	N
R/K	0.0622	likely_benign	0.0649	benign	-0.797	Destabilizing	None	N	0.081	neutral	N	0.493826365	None	None	N
R/L	0.1189	likely_benign	0.1265	benign	-0.175	Destabilizing	0.007	N	0.258	neutral	None	None	None	None	N
R/M	0.1078	likely_benign	0.1143	benign	-0.294	Destabilizing	0.356	N	0.291	neutral	None	None	None	None	N
R/N	0.2101	likely_benign	0.2337	benign	-0.181	Destabilizing	0.031	N	0.211	neutral	None	None	None	None	N
R/P	0.6492	likely_pathogenic	0.6807	pathogenic	-0.369	Destabilizing	0.136	N	0.389	neutral	None	None	None	None	N
R/Q	0.0717	likely_benign	0.0729	benign	-0.494	Destabilizing	0.001	N	0.089	neutral	None	None	None	None	N
R/S	0.1561	likely_benign	0.1762	benign	-0.955	Destabilizing	0.012	N	0.271	neutral	N	0.493250362	None	None	N
R/T	0.0818	likely_benign	0.0855	benign	-0.724	Destabilizing	None	N	0.115	neutral	N	0.509643967	None	None	N
R/V	0.1381	likely_benign	0.1493	benign	-0.369	Destabilizing	0.016	N	0.309	neutral	None	None	None	None	N
R/W	0.1359	likely_benign	0.137	benign	-0.664	Destabilizing	0.864	D	0.326	neutral	None	None	None	None	N
R/Y	0.2198	likely_benign	0.2328	benign	-0.329	Destabilizing	0.356	N	0.39	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.