TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31628	95107;95108;95109	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
N2AB	29987	90184;90185;90186	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
N2A	29060	87403;87404;87405	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
N2B	22563	67912;67913;67914	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
Novex-1	22688	68287;68288;68289	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
Novex-2	22755	68488;68489;68490	chr2:178546449;178546448;178546447	chr2:179411176;179411175;179411174
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-152
• Domain position: 8
• Structural Position: 18
• Q(SASA): 0.7532
• 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
R/K	rs1697174649	None	0.906	N	0.435	0.164	0.276482976112	gnomAD-4.0.0	1.59161E-06	None	None	None	None	I	None	0	0	None	0	2.77639E-05	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
R/A	0.7532	likely_pathogenic	0.7347	pathogenic	-0.029	Destabilizing	0.864	D	0.481	neutral	None	None	None	None	I
R/C	0.3954	ambiguous	0.3577	ambiguous	-0.323	Destabilizing	1.0	D	0.481	neutral	None	None	None	None	I
R/D	0.9359	likely_pathogenic	0.9332	pathogenic	-0.2	Destabilizing	0.939	D	0.533	neutral	None	None	None	None	I
R/E	0.7444	likely_pathogenic	0.7276	pathogenic	-0.147	Destabilizing	0.969	D	0.451	neutral	None	None	None	None	I
R/F	0.8174	likely_pathogenic	0.7961	pathogenic	-0.318	Destabilizing	0.999	D	0.477	neutral	None	None	None	None	I
R/G	0.6971	likely_pathogenic	0.6741	pathogenic	-0.192	Destabilizing	0.959	D	0.497	neutral	N	0.50522907	None	None	I
R/H	0.2018	likely_benign	0.1849	benign	-0.624	Destabilizing	0.995	D	0.453	neutral	None	None	None	None	I
R/I	0.6515	likely_pathogenic	0.6275	pathogenic	0.359	Stabilizing	0.988	D	0.484	neutral	N	0.486061631	None	None	I
R/K	0.1901	likely_benign	0.1769	benign	-0.196	Destabilizing	0.906	D	0.435	neutral	N	0.46437025	None	None	I
R/L	0.493	ambiguous	0.4647	ambiguous	0.359	Stabilizing	0.969	D	0.523	neutral	None	None	None	None	I
R/M	0.5859	likely_pathogenic	0.5581	ambiguous	-0.074	Destabilizing	1.0	D	0.476	neutral	None	None	None	None	I
R/N	0.8815	likely_pathogenic	0.8742	pathogenic	-0.098	Destabilizing	0.293	N	0.317	neutral	None	None	None	None	I
R/P	0.756	likely_pathogenic	0.7485	pathogenic	0.249	Stabilizing	0.995	D	0.501	neutral	None	None	None	None	I
R/Q	0.2159	likely_benign	0.1931	benign	-0.158	Destabilizing	0.995	D	0.465	neutral	None	None	None	None	I
R/S	0.842	likely_pathogenic	0.8311	pathogenic	-0.375	Destabilizing	0.476	N	0.339	neutral	D	0.524647918	None	None	I
R/T	0.6325	likely_pathogenic	0.581	pathogenic	-0.201	Destabilizing	0.238	N	0.322	neutral	D	0.52413063	None	None	I
R/V	0.688	likely_pathogenic	0.6646	pathogenic	0.249	Stabilizing	0.969	D	0.495	neutral	None	None	None	None	I
R/W	0.3528	ambiguous	0.311	benign	-0.433	Destabilizing	1.0	D	0.526	neutral	None	None	None	None	I
R/Y	0.6583	likely_pathogenic	0.6325	pathogenic	-0.022	Destabilizing	0.999	D	0.495	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.