TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18445	55558;55559;55560	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
N2AB	16804	50635;50636;50637	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
N2A	15877	47854;47855;47856	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
N2B	9380	28363;28364;28365	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
Novex-1	9505	28738;28739;28740	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
Novex-2	9572	28939;28940;28941	chr2:178601757;178601756;178601755	chr2:179466484;179466483;179466482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-115
• Domain position: 64
• Structural Position: 139
• Q(SASA): 0.1931
• 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
I/V	None	None	None	N	0.231	0.072	0.319970858106	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
I/A	0.3142	likely_benign	0.3321	benign	-2.664	Highly Destabilizing	0.055	N	0.445	neutral	None	None	None	None	N
I/C	0.5652	likely_pathogenic	0.5413	ambiguous	-1.884	Destabilizing	0.883	D	0.564	neutral	None	None	None	None	N
I/D	0.6774	likely_pathogenic	0.7137	pathogenic	-3.072	Highly Destabilizing	0.124	N	0.572	neutral	None	None	None	None	N
I/E	0.5086	ambiguous	0.5321	ambiguous	-2.936	Highly Destabilizing	0.22	N	0.573	neutral	None	None	None	None	N
I/F	0.1691	likely_benign	0.1609	benign	-1.617	Destabilizing	0.427	N	0.556	neutral	N	0.475627394	None	None	N
I/G	0.678	likely_pathogenic	0.6814	pathogenic	-3.1	Highly Destabilizing	0.22	N	0.564	neutral	None	None	None	None	N
I/H	0.3781	ambiguous	0.3894	ambiguous	-2.414	Highly Destabilizing	0.667	D	0.615	neutral	None	None	None	None	N
I/K	0.3588	ambiguous	0.3963	ambiguous	-2.189	Highly Destabilizing	0.22	N	0.571	neutral	None	None	None	None	N
I/L	0.1199	likely_benign	0.1153	benign	-1.428	Destabilizing	0.019	N	0.392	neutral	N	0.470701577	None	None	N
I/M	0.1118	likely_benign	0.1101	benign	-1.315	Destabilizing	0.427	N	0.566	neutral	N	0.503179354	None	None	N
I/N	0.2216	likely_benign	0.2425	benign	-2.298	Highly Destabilizing	0.003	N	0.533	neutral	N	0.521938473	None	None	N
I/P	0.961	likely_pathogenic	0.9698	pathogenic	-1.821	Destabilizing	0.667	D	0.631	neutral	None	None	None	None	N
I/Q	0.3857	ambiguous	0.4016	ambiguous	-2.323	Highly Destabilizing	0.667	D	0.631	neutral	None	None	None	None	N
I/R	0.2694	likely_benign	0.3052	benign	-1.628	Destabilizing	0.497	N	0.632	neutral	None	None	None	None	N
I/S	0.2187	likely_benign	0.2347	benign	-2.883	Highly Destabilizing	0.042	N	0.532	neutral	N	0.468989423	None	None	N
I/T	0.1284	likely_benign	0.1377	benign	-2.64	Highly Destabilizing	0.001	N	0.355	neutral	N	0.405801949	None	None	N
I/V	0.0763	likely_benign	0.0718	benign	-1.821	Destabilizing	None	N	0.231	neutral	N	0.448806152	None	None	N
I/W	0.7447	likely_pathogenic	0.721	pathogenic	-1.939	Destabilizing	0.958	D	0.647	neutral	None	None	None	None	N
I/Y	0.3955	ambiguous	0.4026	ambiguous	-1.748	Destabilizing	0.667	D	0.587	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.