TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31334	94225;94226;94227	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
N2AB	29693	89302;89303;89304	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
N2A	28766	86521;86522;86523	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
N2B	22269	67030;67031;67032	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
Novex-1	22394	67405;67406;67407	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
Novex-2	22461	67606;67607;67608	chr2:178547626;178547625;178547624	chr2:179412353;179412352;179412351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-116
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.8319
• 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
K/T	None	None	None	N	0.141	0.127	0.261217442401	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.1217	likely_benign	0.123	benign	0.101	Stabilizing	None	N	0.141	neutral	None	None	None	None	I
K/C	0.4588	ambiguous	0.4736	ambiguous	-0.146	Destabilizing	0.628	D	0.264	neutral	None	None	None	None	I
K/D	0.2405	likely_benign	0.2416	benign	-0.054	Destabilizing	0.016	N	0.28	neutral	None	None	None	None	I
K/E	0.0711	likely_benign	0.0782	benign	-0.059	Destabilizing	None	N	0.137	neutral	N	0.40746567	None	None	I
K/F	0.5083	ambiguous	0.5408	ambiguous	-0.155	Destabilizing	0.356	N	0.355	neutral	None	None	None	None	I
K/G	0.2032	likely_benign	0.2012	benign	-0.073	Destabilizing	0.031	N	0.273	neutral	None	None	None	None	I
K/H	0.2369	likely_benign	0.234	benign	-0.299	Destabilizing	0.214	N	0.301	neutral	None	None	None	None	I
K/I	0.1543	likely_benign	0.1613	benign	0.476	Stabilizing	0.029	N	0.449	neutral	N	0.479464628	None	None	I
K/L	0.1572	likely_benign	0.1661	benign	0.476	Stabilizing	0.016	N	0.261	neutral	None	None	None	None	I
K/M	0.1338	likely_benign	0.1397	benign	0.203	Stabilizing	0.356	N	0.301	neutral	None	None	None	None	I
K/N	0.201	likely_benign	0.214	benign	0.301	Stabilizing	0.024	N	0.298	neutral	N	0.506341798	None	None	I
K/P	0.3475	ambiguous	0.3482	ambiguous	0.377	Stabilizing	0.136	N	0.44	neutral	None	None	None	None	I
K/Q	0.0914	likely_benign	0.0925	benign	0.127	Stabilizing	None	N	0.24	neutral	N	0.478424478	None	None	I
K/R	0.0793	likely_benign	0.0799	benign	0.032	Stabilizing	0.012	N	0.345	neutral	N	0.483926298	None	None	I
K/S	0.1658	likely_benign	0.1683	benign	-0.12	Destabilizing	None	N	0.123	neutral	None	None	None	None	I
K/T	0.0898	likely_benign	0.0932	benign	0.009	Stabilizing	None	N	0.141	neutral	N	0.481059351	None	None	I
K/V	0.1262	likely_benign	0.1294	benign	0.377	Stabilizing	0.016	N	0.289	neutral	None	None	None	None	I
K/W	0.5927	likely_pathogenic	0.6172	pathogenic	-0.214	Destabilizing	0.864	D	0.247	neutral	None	None	None	None	I
K/Y	0.4465	ambiguous	0.4592	ambiguous	0.146	Stabilizing	0.356	N	0.369	neutral	None	None	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.