TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6452	19579;19580;19581	chr2:178728572;178728571;178728570	chr2:179593299;179593298;179593297
N2AB	6135	18628;18629;18630	chr2:178728572;178728571;178728570	chr2:179593299;179593298;179593297
N2A	5208	15847;15848;15849	chr2:178728572;178728571;178728570	chr2:179593299;179593298;179593297
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-48
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2903
• 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
S/G	rs1352966588	None	0.906	N	0.479	0.384	0.376745185316	gnomAD-4.0.0	1.36899E-05	None	None	None	None	N	None	0	0	None	0	2.52564E-05	None	0	0	1.43949E-05	0	4.97331E-05
S/R	rs369275615	None	0.936	N	0.503	0.393	0.143124449307	gnomAD-4.0.0	6.84557E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.16012E-05	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	0.0862	likely_benign	0.0914	benign	-0.512	Destabilizing	0.863	D	0.387	neutral	None	None	None	None	N
S/C	0.2075	likely_benign	0.25	benign	-0.348	Destabilizing	0.999	D	0.513	neutral	D	0.5371753	None	None	N
S/D	0.6057	likely_pathogenic	0.6048	pathogenic	0.341	Stabilizing	0.759	D	0.481	neutral	None	None	None	None	N
S/E	0.6143	likely_pathogenic	0.6444	pathogenic	0.287	Stabilizing	0.079	N	0.107	neutral	None	None	None	None	N
S/F	0.4339	ambiguous	0.4601	ambiguous	-0.906	Destabilizing	0.997	D	0.592	neutral	None	None	None	None	N
S/G	0.115	likely_benign	0.1243	benign	-0.69	Destabilizing	0.906	D	0.479	neutral	N	0.495749323	None	None	N
S/H	0.5836	likely_pathogenic	0.6401	pathogenic	-1.17	Destabilizing	0.997	D	0.531	neutral	None	None	None	None	N
S/I	0.279	likely_benign	0.3562	ambiguous	-0.163	Destabilizing	0.976	D	0.557	neutral	N	0.502434821	None	None	N
S/K	0.7705	likely_pathogenic	0.8287	pathogenic	-0.444	Destabilizing	0.17	N	0.161	neutral	None	None	None	None	N
S/L	0.1824	likely_benign	0.1871	benign	-0.163	Destabilizing	0.939	D	0.525	neutral	None	None	None	None	N
S/M	0.2996	likely_benign	0.3192	benign	0.047	Stabilizing	0.997	D	0.524	neutral	None	None	None	None	N
S/N	0.2707	likely_benign	0.2786	benign	-0.247	Destabilizing	0.959	D	0.503	neutral	N	0.517714692	None	None	N
S/P	0.8817	likely_pathogenic	0.8898	pathogenic	-0.247	Destabilizing	0.99	D	0.511	neutral	None	None	None	None	N
S/Q	0.6331	likely_pathogenic	0.685	pathogenic	-0.444	Destabilizing	0.939	D	0.491	neutral	None	None	None	None	N
S/R	0.6279	likely_pathogenic	0.7064	pathogenic	-0.32	Destabilizing	0.936	D	0.503	neutral	N	0.499610437	None	None	N
S/T	0.115	likely_benign	0.1148	benign	-0.363	Destabilizing	0.134	N	0.155	neutral	D	0.531424748	None	None	N
S/V	0.3027	likely_benign	0.3624	ambiguous	-0.247	Destabilizing	0.939	D	0.515	neutral	None	None	None	None	N
S/W	0.612	likely_pathogenic	0.6477	pathogenic	-0.869	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
S/Y	0.4069	ambiguous	0.4342	ambiguous	-0.596	Destabilizing	0.997	D	0.592	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.