TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25913	77962;77963;77964	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
N2AB	24272	73039;73040;73041	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
N2A	23345	70258;70259;70260	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
N2B	16848	50767;50768;50769	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
Novex-1	16973	51142;51143;51144	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
Novex-2	17040	51343;51344;51345	chr2:178568395;178568394;178568393	chr2:179433122;179433121;179433120
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-76
• Domain position: 24
• Structural Position: 25
• Q(SASA): 0.5623
• Predicted PPI site: I

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
N/I	None	None	0.093	N	0.564	0.259	0.496495002422	gnomAD-4.0.0	1.59264E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85997E-06	0	0
N/K	None	None	None	N	0.119	0.11	0.0138822411134	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
N/A	0.1079	likely_benign	0.1201	benign	-0.81	Destabilizing	0.016	N	0.349	neutral	None	None	None	None	I
N/C	0.1578	likely_benign	0.1525	benign	0.067	Stabilizing	0.864	D	0.477	neutral	None	None	None	None	I
N/D	0.0798	likely_benign	0.0876	benign	-0.581	Destabilizing	None	N	0.11	neutral	N	0.405156083	None	None	I
N/E	0.1153	likely_benign	0.1281	benign	-0.497	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
N/F	0.2562	likely_benign	0.2879	benign	-0.547	Destabilizing	0.356	N	0.488	neutral	None	None	None	None	I
N/G	0.1654	likely_benign	0.185	benign	-1.149	Destabilizing	0.031	N	0.335	neutral	None	None	None	None	I
N/H	0.0839	likely_benign	0.0853	benign	-0.948	Destabilizing	0.171	N	0.454	neutral	N	0.510150107	None	None	I
N/I	0.1053	likely_benign	0.1207	benign	0.051	Stabilizing	0.093	N	0.564	neutral	N	0.485195734	None	None	I
N/K	0.1436	likely_benign	0.1618	benign	-0.384	Destabilizing	None	N	0.119	neutral	N	0.406540163	None	None	I
N/L	0.0976	likely_benign	0.0984	benign	0.051	Stabilizing	0.038	N	0.464	neutral	None	None	None	None	I
N/M	0.141	likely_benign	0.14	benign	0.495	Stabilizing	0.356	N	0.492	neutral	None	None	None	None	I
N/P	0.6723	likely_pathogenic	0.7246	pathogenic	-0.206	Destabilizing	0.136	N	0.575	neutral	None	None	None	None	I
N/Q	0.128	likely_benign	0.1355	benign	-0.901	Destabilizing	None	N	0.213	neutral	None	None	None	None	I
N/R	0.2114	likely_benign	0.2439	benign	-0.424	Destabilizing	0.038	N	0.317	neutral	None	None	None	None	I
N/S	0.0719	likely_benign	0.0752	benign	-0.894	Destabilizing	0.012	N	0.314	neutral	N	0.400459552	None	None	I
N/T	0.0845	likely_benign	0.0931	benign	-0.624	Destabilizing	None	N	0.145	neutral	N	0.428992948	None	None	I
N/V	0.1147	likely_benign	0.1293	benign	-0.206	Destabilizing	0.038	N	0.469	neutral	None	None	None	None	I
N/W	0.5441	ambiguous	0.5853	pathogenic	-0.339	Destabilizing	0.864	D	0.495	neutral	None	None	None	None	I
N/Y	0.0991	likely_benign	0.1039	benign	-0.148	Destabilizing	0.295	N	0.519	neutral	N	0.488505398	None	None	I

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.