TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9999	30220;30221;30222	chr2:178704375;178704374;178704373	chr2:179569102;179569101;179569100
N2AB	9682	29269;29270;29271	chr2:178704375;178704374;178704373	chr2:179569102;179569101;179569100
N2A	8755	26488;26489;26490	chr2:178704375;178704374;178704373	chr2:179569102;179569101;179569100
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-85
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.4521
• 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/A	rs776483588	-0.416	0.001	None	0.09	0.078	0.154104182512	gnomAD-2.1.1	4.01E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
T/A	rs776483588	-0.416	0.001	None	0.09	0.078	0.154104182512	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.82E-05	0	0	0	0	None	0	0	0	0	0
T/A	rs776483588	-0.416	0.001	None	0.09	0.078	0.154104182512	gnomAD-4.0.0	3.84321E-06	None	None	None	None	N	None	5.07237E-05	0	None	0	0	None	0	0	0	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
T/A	0.1083	likely_benign	0.1187	benign	-0.426	Destabilizing	0.001	N	0.09	neutral	None	None	None	None	N
T/C	0.5576	ambiguous	0.6061	pathogenic	-0.458	Destabilizing	0.951	D	0.422	neutral	None	None	None	None	N
T/D	0.5193	ambiguous	0.5307	ambiguous	0.167	Stabilizing	0.418	N	0.359	neutral	None	None	None	None	N
T/E	0.4025	ambiguous	0.4081	ambiguous	0.144	Stabilizing	0.264	N	0.365	neutral	None	None	None	None	N
T/F	0.2667	likely_benign	0.2599	benign	-0.609	Destabilizing	0.716	D	0.478	neutral	None	None	None	None	N
T/G	0.4399	ambiguous	0.4851	ambiguous	-0.638	Destabilizing	0.129	N	0.341	neutral	None	None	None	None	N
T/H	0.288	likely_benign	0.2938	benign	-0.851	Destabilizing	0.836	D	0.439	neutral	None	None	None	None	N
T/I	0.1786	likely_benign	0.1774	benign	0.027	Stabilizing	0.002	N	0.226	neutral	None	None	None	None	N
T/K	0.2906	likely_benign	0.2704	benign	-0.544	Destabilizing	0.264	N	0.375	neutral	None	None	None	None	N
T/L	0.1297	likely_benign	0.1334	benign	0.027	Stabilizing	0.049	N	0.377	neutral	None	None	None	None	N
T/M	0.1094	likely_benign	0.1143	benign	-0.017	Destabilizing	0.716	D	0.434	neutral	None	None	None	None	N
T/N	0.1763	likely_benign	0.1792	benign	-0.463	Destabilizing	0.351	N	0.329	neutral	None	None	None	None	N
T/P	0.2842	likely_benign	0.3217	benign	-0.092	Destabilizing	0.523	D	0.473	neutral	None	None	None	None	N
T/Q	0.2879	likely_benign	0.2918	benign	-0.59	Destabilizing	0.061	N	0.233	neutral	None	None	None	None	N
T/R	0.218	likely_benign	0.2049	benign	-0.311	Destabilizing	0.418	N	0.465	neutral	None	None	None	None	N
T/S	0.1429	likely_benign	0.1526	benign	-0.7	Destabilizing	0.003	N	0.087	neutral	None	None	None	None	N
T/V	0.1548	likely_benign	0.1606	benign	-0.092	Destabilizing	0.049	N	0.315	neutral	None	None	None	None	N
T/W	0.6409	likely_pathogenic	0.649	pathogenic	-0.61	Destabilizing	0.983	D	0.474	neutral	None	None	None	None	N
T/Y	0.3184	likely_benign	0.3227	benign	-0.345	Destabilizing	0.836	D	0.481	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.