TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19468	58627;58628;58629	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
N2AB	17827	53704;53705;53706	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
N2A	16900	50923;50924;50925	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
N2B	10403	31432;31433;31434	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
Novex-1	10528	31807;31808;31809	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
Novex-2	10595	32008;32009;32010	chr2:178593991;178593990;178593989	chr2:179458718;179458717;179458716
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Ig-118
• Domain position: 78
• Structural Position: 166
• Q(SASA): 0.8029
• 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
R/G	rs2050849448	None	0.217	N	0.485	0.279	0.431379191433	gnomAD-4.0.0	1.5919E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43386E-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
R/A	0.5845	likely_pathogenic	0.5222	ambiguous	-0.013	Destabilizing	0.992	D	0.612	neutral	None	None	None	None	I
R/C	0.223	likely_benign	0.1815	benign	-0.306	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
R/D	0.8914	likely_pathogenic	0.8571	pathogenic	-0.234	Destabilizing	0.999	D	0.596	neutral	None	None	None	None	I
R/E	0.6023	likely_pathogenic	0.4993	ambiguous	-0.189	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
R/F	0.7705	likely_pathogenic	0.7077	pathogenic	-0.32	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
R/G	0.58	likely_pathogenic	0.4793	ambiguous	-0.164	Destabilizing	0.217	N	0.485	neutral	N	0.493454691	None	None	I
R/H	0.2204	likely_benign	0.1791	benign	-0.597	Destabilizing	1.0	D	0.634	neutral	None	None	None	None	I
R/I	0.4123	ambiguous	0.3436	ambiguous	0.341	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
R/K	0.1792	likely_benign	0.1596	benign	-0.19	Destabilizing	0.987	D	0.549	neutral	N	0.489055264	None	None	I
R/L	0.4471	ambiguous	0.3715	ambiguous	0.341	Stabilizing	1.0	D	0.581	neutral	None	None	None	None	I
R/M	0.4535	ambiguous	0.3666	ambiguous	-0.075	Destabilizing	1.0	D	0.611	neutral	N	0.50045613	None	None	I
R/N	0.8141	likely_pathogenic	0.7742	pathogenic	-0.09	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
R/P	0.9783	likely_pathogenic	0.9649	pathogenic	0.242	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	I
R/Q	0.1396	likely_benign	0.1128	benign	-0.151	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
R/S	0.7291	likely_pathogenic	0.6521	pathogenic	-0.339	Destabilizing	0.989	D	0.629	neutral	N	0.520300891	None	None	I
R/T	0.4505	ambiguous	0.3671	ambiguous	-0.18	Destabilizing	0.998	D	0.605	neutral	N	0.49136485	None	None	I
R/V	0.4628	ambiguous	0.4028	ambiguous	0.242	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
R/W	0.3879	ambiguous	0.2904	benign	-0.456	Destabilizing	1.0	D	0.703	prob.neutral	N	0.512319414	None	None	I
R/Y	0.6219	likely_pathogenic	0.5418	ambiguous	-0.046	Destabilizing	1.0	D	0.653	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.