TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14903	44932;44933;44934	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
N2AB	13262	40009;40010;40011	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
N2A	12335	37228;37229;37230	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
N2B	5838	17737;17738;17739	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
Novex-1	5963	18112;18113;18114	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
Novex-2	6030	18313;18314;18315	chr2:178624573;178624572;178624571	chr2:179489300;179489299;179489298
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-100
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.6273
• 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
D/Y	None	None	1.0	D	0.74	0.456	0.75049894695	gnomAD-4.0.0	1.59344E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.4332E-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
D/A	0.2246	likely_benign	0.1599	benign	-0.123	Destabilizing	0.977	D	0.601	neutral	D	0.551837373	None	None	N
D/C	0.752	likely_pathogenic	0.709	pathogenic	0.074	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
D/E	0.1763	likely_benign	0.129	benign	-0.259	Destabilizing	0.117	N	0.261	neutral	N	0.467020121	None	None	N
D/F	0.7071	likely_pathogenic	0.6346	pathogenic	-0.143	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	N
D/G	0.2699	likely_benign	0.2227	benign	-0.294	Destabilizing	0.977	D	0.594	neutral	D	0.534892106	None	None	N
D/H	0.3894	ambiguous	0.3192	benign	0.116	Stabilizing	0.999	D	0.683	prob.neutral	D	0.565116809	None	None	N
D/I	0.4382	ambiguous	0.3527	ambiguous	0.269	Stabilizing	0.998	D	0.749	deleterious	None	None	None	None	N
D/K	0.3865	ambiguous	0.3331	benign	0.436	Stabilizing	0.99	D	0.625	neutral	None	None	None	None	N
D/L	0.5181	ambiguous	0.4322	ambiguous	0.269	Stabilizing	0.995	D	0.726	prob.delet.	None	None	None	None	N
D/M	0.7284	likely_pathogenic	0.6529	pathogenic	0.299	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
D/N	0.131	likely_benign	0.1038	benign	0.173	Stabilizing	0.993	D	0.601	neutral	N	0.510168819	None	None	N
D/P	0.8945	likely_pathogenic	0.8904	pathogenic	0.16	Stabilizing	0.998	D	0.651	neutral	None	None	None	None	N
D/Q	0.3947	ambiguous	0.3132	benign	0.193	Stabilizing	0.99	D	0.655	neutral	None	None	None	None	N
D/R	0.4641	ambiguous	0.4149	ambiguous	0.59	Stabilizing	0.995	D	0.691	prob.neutral	None	None	None	None	N
D/S	0.1599	likely_benign	0.125	benign	0.076	Stabilizing	0.983	D	0.559	neutral	None	None	None	None	N
D/T	0.303	likely_benign	0.2491	benign	0.208	Stabilizing	0.995	D	0.633	neutral	None	None	None	None	N
D/V	0.2475	likely_benign	0.1889	benign	0.16	Stabilizing	0.997	D	0.722	prob.delet.	D	0.536602571	None	None	N
D/W	0.9152	likely_pathogenic	0.9005	pathogenic	-0.056	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/Y	0.3268	likely_benign	0.2729	benign	0.09	Stabilizing	1.0	D	0.74	deleterious	D	0.665026455	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.