TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15342	46249;46250;46251	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
N2AB	13701	41326;41327;41328	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
N2A	12774	38545;38546;38547	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
N2B	6277	19054;19055;19056	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
Novex-1	6402	19429;19430;19431	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
Novex-2	6469	19630;19631;19632	chr2:178620497;178620496;178620495	chr2:179485224;179485223;179485222
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-105
• Domain position: 41
• Structural Position: 59
• Q(SASA): 0.5202
• 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
P/H	rs2154211069	None	0.828	N	0.393	0.187	0.411265580357	gnomAD-4.0.0	1.59417E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86372E-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
P/A	0.0827	likely_benign	0.0754	benign	-0.568	Destabilizing	None	N	0.155	neutral	N	0.453364899	None	None	N
P/C	0.365	ambiguous	0.3987	ambiguous	-0.709	Destabilizing	0.676	D	0.408	neutral	None	None	None	None	N
P/D	0.3293	likely_benign	0.3318	benign	-0.52	Destabilizing	0.072	N	0.396	neutral	None	None	None	None	N
P/E	0.2591	likely_benign	0.2525	benign	-0.587	Destabilizing	0.072	N	0.339	neutral	None	None	None	None	N
P/F	0.3568	ambiguous	0.374	ambiguous	-0.645	Destabilizing	0.356	N	0.43	neutral	None	None	None	None	N
P/G	0.207	likely_benign	0.202	benign	-0.727	Destabilizing	0.038	N	0.377	neutral	None	None	None	None	N
P/H	0.1634	likely_benign	0.154	benign	-0.174	Destabilizing	0.828	D	0.393	neutral	N	0.486766999	None	None	N
P/I	0.1812	likely_benign	0.1935	benign	-0.273	Destabilizing	0.038	N	0.397	neutral	None	None	None	None	N
P/K	0.1792	likely_benign	0.1751	benign	-0.567	Destabilizing	0.072	N	0.338	neutral	None	None	None	None	N
P/L	0.1114	likely_benign	0.1019	benign	-0.273	Destabilizing	0.012	N	0.397	neutral	N	0.476948943	None	None	N
P/M	0.2437	likely_benign	0.2439	benign	-0.543	Destabilizing	0.356	N	0.401	neutral	None	None	None	None	N
P/N	0.2108	likely_benign	0.2152	benign	-0.426	Destabilizing	0.214	N	0.415	neutral	None	None	None	None	N
P/Q	0.1521	likely_benign	0.1389	benign	-0.596	Destabilizing	0.356	N	0.385	neutral	None	None	None	None	N
P/R	0.1429	likely_benign	0.1347	benign	-0.086	Destabilizing	0.171	N	0.413	neutral	N	0.456172755	None	None	N
P/S	0.1027	likely_benign	0.1	benign	-0.759	Destabilizing	0.012	N	0.323	neutral	N	0.478852168	None	None	N
P/T	0.0837	likely_benign	0.0859	benign	-0.722	Destabilizing	None	N	0.149	neutral	N	0.350511057	None	None	N
P/V	0.1426	likely_benign	0.1442	benign	-0.339	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
P/W	0.543	ambiguous	0.5696	pathogenic	-0.756	Destabilizing	0.864	D	0.449	neutral	None	None	None	None	N
P/Y	0.341	ambiguous	0.3605	ambiguous	-0.464	Destabilizing	0.356	N	0.425	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.