TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4993	15202;15203;15204	chr2:178734947;178734946;178734945	chr2:179599674;179599673;179599672
N2AB	4676	14251;14252;14253	chr2:178734947;178734946;178734945	chr2:179599674;179599673;179599672
N2A	3749	11470;11471;11472	chr2:178734947;178734946;178734945	chr2:179599674;179599673;179599672
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: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-33
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.2576
• 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
M/I	None	None	0.028	N	0.279	0.122	0.419713421852	gnomAD-4.0.0	1.60967E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.89059E-06	0	0
M/V	None	None	0.001	N	0.117	0.151	0.298745278005	gnomAD-4.0.0	1.61024E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44923E-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
M/A	0.6477	likely_pathogenic	0.7547	pathogenic	-2.161	Highly Destabilizing	0.07	N	0.275	neutral	None	None	None	None	I
M/C	0.8588	likely_pathogenic	0.8988	pathogenic	-1.862	Destabilizing	0.901	D	0.406	neutral	None	None	None	None	I
M/D	0.9817	likely_pathogenic	0.9894	pathogenic	-1.344	Destabilizing	0.722	D	0.551	neutral	None	None	None	None	I
M/E	0.8842	likely_pathogenic	0.9263	pathogenic	-1.213	Destabilizing	0.46	N	0.398	neutral	None	None	None	None	I
M/F	0.4824	ambiguous	0.5554	ambiguous	-0.735	Destabilizing	0.08	N	0.34	neutral	None	None	None	None	I
M/G	0.8663	likely_pathogenic	0.9076	pathogenic	-2.567	Highly Destabilizing	0.26	N	0.381	neutral	None	None	None	None	I
M/H	0.7713	likely_pathogenic	0.8405	pathogenic	-1.81	Destabilizing	0.901	D	0.465	neutral	None	None	None	None	I
M/I	0.503	ambiguous	0.6202	pathogenic	-1.04	Destabilizing	0.028	N	0.279	neutral	N	0.39830955	None	None	I
M/K	0.3984	ambiguous	0.5091	ambiguous	-1.299	Destabilizing	0.21	N	0.371	neutral	N	0.466000906	None	None	I
M/L	0.0868	likely_benign	0.1054	benign	-1.04	Destabilizing	None	N	0.103	neutral	N	0.362232886	None	None	I
M/N	0.8978	likely_pathogenic	0.9363	pathogenic	-1.351	Destabilizing	0.722	D	0.492	neutral	None	None	None	None	I
M/P	0.9631	likely_pathogenic	0.9839	pathogenic	-1.391	Destabilizing	0.722	D	0.505	neutral	None	None	None	None	I
M/Q	0.4865	ambiguous	0.5832	pathogenic	-1.254	Destabilizing	0.722	D	0.387	neutral	None	None	None	None	I
M/R	0.4304	ambiguous	0.5241	ambiguous	-0.984	Destabilizing	0.391	N	0.439	neutral	N	0.456861703	None	None	I
M/S	0.7645	likely_pathogenic	0.8274	pathogenic	-1.985	Destabilizing	0.26	N	0.379	neutral	None	None	None	None	I
M/T	0.5776	likely_pathogenic	0.7024	pathogenic	-1.742	Destabilizing	0.116	N	0.349	neutral	N	0.434072639	None	None	I
M/V	0.155	likely_benign	0.2088	benign	-1.391	Destabilizing	0.001	N	0.117	neutral	N	0.259962311	None	None	I
M/W	0.8378	likely_pathogenic	0.8868	pathogenic	-0.85	Destabilizing	None	N	0.174	neutral	None	None	None	None	I
M/Y	0.762	likely_pathogenic	0.8267	pathogenic	-0.897	Destabilizing	0.148	N	0.393	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.