TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23293	70102;70103;70104	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
N2AB	21652	65179;65180;65181	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
N2A	20725	62398;62399;62400	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
N2B	14228	42907;42908;42909	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
Novex-1	14353	43282;43283;43284	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
Novex-2	14420	43483;43484;43485	chr2:178576255;178576254;178576253	chr2:179440982;179440981;179440980
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Fn3-57
• Domain position: 54
• Structural Position: 71
• Q(SASA): 0.4193
• 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
G/R	None	None	0.942	N	0.439	0.312	0.622080263406	gnomAD-4.0.0	1.59617E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43881E-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
G/A	0.196	likely_benign	0.1893	benign	-0.305	Destabilizing	0.656	D	0.375	neutral	N	0.474997383	None	None	I
G/C	0.3614	ambiguous	0.3285	benign	-0.955	Destabilizing	0.998	D	0.57	neutral	None	None	None	None	I
G/D	0.2753	likely_benign	0.2528	benign	-0.544	Destabilizing	0.754	D	0.359	neutral	None	None	None	None	I
G/E	0.2791	likely_benign	0.2552	benign	-0.69	Destabilizing	0.014	N	0.282	neutral	N	0.445559911	None	None	I
G/F	0.7781	likely_pathogenic	0.7331	pathogenic	-1.051	Destabilizing	0.993	D	0.541	neutral	None	None	None	None	I
G/H	0.5268	ambiguous	0.4677	ambiguous	-0.394	Destabilizing	0.994	D	0.473	neutral	None	None	None	None	I
G/I	0.4726	ambiguous	0.4522	ambiguous	-0.567	Destabilizing	0.956	D	0.544	neutral	None	None	None	None	I
G/K	0.4768	ambiguous	0.4224	ambiguous	-0.611	Destabilizing	0.754	D	0.441	neutral	None	None	None	None	I
G/L	0.5939	likely_pathogenic	0.5426	ambiguous	-0.567	Destabilizing	0.956	D	0.515	neutral	None	None	None	None	I
G/M	0.6375	likely_pathogenic	0.5929	pathogenic	-0.696	Destabilizing	0.998	D	0.537	neutral	None	None	None	None	I
G/N	0.34	likely_benign	0.3109	benign	-0.32	Destabilizing	0.86	D	0.383	neutral	None	None	None	None	I
G/P	0.7448	likely_pathogenic	0.7205	pathogenic	-0.459	Destabilizing	0.978	D	0.477	neutral	None	None	None	None	I
G/Q	0.3991	ambiguous	0.3543	ambiguous	-0.556	Destabilizing	0.193	N	0.283	neutral	None	None	None	None	I
G/R	0.3953	ambiguous	0.3488	ambiguous	-0.26	Destabilizing	0.942	D	0.439	neutral	N	0.477133612	None	None	I
G/S	0.1488	likely_benign	0.1427	benign	-0.479	Destabilizing	0.754	D	0.353	neutral	None	None	None	None	I
G/T	0.2406	likely_benign	0.2284	benign	-0.563	Destabilizing	0.076	N	0.284	neutral	None	None	None	None	I
G/V	0.3195	likely_benign	0.3032	benign	-0.459	Destabilizing	0.942	D	0.517	neutral	N	0.43799922	None	None	I
G/W	0.6613	likely_pathogenic	0.609	pathogenic	-1.132	Destabilizing	0.998	D	0.544	neutral	None	None	None	None	I
G/Y	0.6335	likely_pathogenic	0.5667	pathogenic	-0.847	Destabilizing	0.993	D	0.551	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.