TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8065	24418;24419;24420	chr2:178719197;178719196;178719195	chr2:179583924;179583923;179583922
N2AB	7748	23467;23468;23469	chr2:178719197;178719196;178719195	chr2:179583924;179583923;179583922
N2A	6821	20686;20687;20688	chr2:178719197;178719196;178719195	chr2:179583924;179583923;179583922
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: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-65
• Domain position: 81
• Structural Position: 165
• Q(SASA): 0.5625
• 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
S/P	rs2077961175	None	0.106	N	0.509	0.273	0.33440975612	gnomAD-4.0.0	1.59144E-06	None	None	None	None	I	None	5.65675E-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
S/A	0.0924	likely_benign	0.1052	benign	-0.444	Destabilizing	0.005	N	0.225	neutral	N	0.515935221	None	None	I
S/C	0.1511	likely_benign	0.1564	benign	-0.344	Destabilizing	0.828	D	0.502	neutral	N	0.520183454	None	None	I
S/D	0.3254	likely_benign	0.3514	ambiguous	-0.225	Destabilizing	None	N	0.127	neutral	None	None	None	None	I
S/E	0.3534	ambiguous	0.3628	ambiguous	-0.309	Destabilizing	0.016	N	0.297	neutral	None	None	None	None	I
S/F	0.1834	likely_benign	0.2252	benign	-0.92	Destabilizing	0.295	N	0.563	neutral	N	0.493685408	None	None	I
S/G	0.1204	likely_benign	0.1243	benign	-0.586	Destabilizing	0.031	N	0.289	neutral	None	None	None	None	I
S/H	0.2456	likely_benign	0.2434	benign	-1.106	Destabilizing	0.214	N	0.515	neutral	None	None	None	None	I
S/I	0.1811	likely_benign	0.2063	benign	-0.194	Destabilizing	0.001	N	0.407	neutral	None	None	None	None	I
S/K	0.3617	ambiguous	0.3605	ambiguous	-0.702	Destabilizing	0.016	N	0.276	neutral	None	None	None	None	I
S/L	0.1111	likely_benign	0.1343	benign	-0.194	Destabilizing	0.016	N	0.566	neutral	None	None	None	None	I
S/M	0.1962	likely_benign	0.2196	benign	0.129	Stabilizing	0.356	N	0.513	neutral	None	None	None	None	I
S/N	0.1196	likely_benign	0.1269	benign	-0.432	Destabilizing	0.038	N	0.297	neutral	None	None	None	None	I
S/P	0.6341	likely_pathogenic	0.7379	pathogenic	-0.247	Destabilizing	0.106	N	0.509	neutral	N	0.506104897	None	None	I
S/Q	0.3061	likely_benign	0.2889	benign	-0.722	Destabilizing	None	N	0.181	neutral	None	None	None	None	I
S/R	0.2761	likely_benign	0.2797	benign	-0.427	Destabilizing	None	N	0.298	neutral	None	None	None	None	I
S/T	0.0822	likely_benign	0.0899	benign	-0.51	Destabilizing	0.001	N	0.122	neutral	N	0.458735144	None	None	I
S/V	0.1876	likely_benign	0.2161	benign	-0.247	Destabilizing	0.016	N	0.557	neutral	None	None	None	None	I
S/W	0.3093	likely_benign	0.3136	benign	-0.905	Destabilizing	0.864	D	0.58	neutral	None	None	None	None	I
S/Y	0.1654	likely_benign	0.1879	benign	-0.652	Destabilizing	0.295	N	0.569	neutral	N	0.515321609	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.