TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14913	44962;44963;44964	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
N2AB	13272	40039;40040;40041	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
N2A	12345	37258;37259;37260	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
N2B	5848	17767;17768;17769	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
Novex-1	5973	18142;18143;18144	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
Novex-2	6040	18343;18344;18345	chr2:178624543;178624542;178624541	chr2:179489270;179489269;179489268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-100
• Domain position: 61
• Structural Position: 143
• Q(SASA): 0.5683
• 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/G	None	None	None	N	0.125	0.069	0.0138822411134	gnomAD-4.0.0	6.16141E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09877E-06	0	0
D/N	None	None	None	N	0.243	0.128	0.0482279557977	gnomAD-4.0.0	3.18682E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72452E-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
D/A	0.17	likely_benign	0.1538	benign	-0.204	Destabilizing	0.027	N	0.324	neutral	N	0.325315128	None	None	N
D/C	0.4991	ambiguous	0.4426	ambiguous	0.332	Stabilizing	0.935	D	0.483	neutral	None	None	None	None	N
D/E	0.1864	likely_benign	0.1824	benign	-0.292	Destabilizing	0.002	N	0.215	neutral	N	0.344406562	None	None	N
D/F	0.6311	likely_pathogenic	0.5754	pathogenic	-0.491	Destabilizing	0.791	D	0.443	neutral	None	None	None	None	N
D/G	0.078	likely_benign	0.0713	benign	-0.379	Destabilizing	None	N	0.125	neutral	N	0.3440864	None	None	N
D/H	0.2734	likely_benign	0.2346	benign	-0.571	Destabilizing	0.317	N	0.352	neutral	N	0.314247692	None	None	N
D/I	0.5201	ambiguous	0.4517	ambiguous	0.197	Stabilizing	0.555	D	0.456	neutral	None	None	None	None	N
D/K	0.3313	likely_benign	0.319	benign	0.356	Stabilizing	0.081	N	0.295	neutral	None	None	None	None	N
D/L	0.4371	ambiguous	0.3953	ambiguous	0.197	Stabilizing	0.38	N	0.428	neutral	None	None	None	None	N
D/M	0.7065	likely_pathogenic	0.6875	pathogenic	0.554	Stabilizing	0.935	D	0.44	neutral	None	None	None	None	N
D/N	0.0964	likely_benign	0.0941	benign	0.238	Stabilizing	None	N	0.243	neutral	N	0.345251468	None	None	N
D/P	0.848	likely_pathogenic	0.83	pathogenic	0.085	Stabilizing	0.555	D	0.347	neutral	None	None	None	None	N
D/Q	0.3098	likely_benign	0.2931	benign	0.239	Stabilizing	0.38	N	0.329	neutral	None	None	None	None	N
D/R	0.325	likely_benign	0.279	benign	0.316	Stabilizing	0.38	N	0.407	neutral	None	None	None	None	N
D/S	0.1045	likely_benign	0.0977	benign	0.117	Stabilizing	0.035	N	0.252	neutral	None	None	None	None	N
D/T	0.2873	likely_benign	0.2659	benign	0.244	Stabilizing	0.081	N	0.351	neutral	None	None	None	None	N
D/V	0.3738	ambiguous	0.3194	benign	0.085	Stabilizing	0.484	N	0.427	neutral	N	0.401461749	None	None	N
D/W	0.83	likely_pathogenic	0.8061	pathogenic	-0.482	Destabilizing	0.935	D	0.56	neutral	None	None	None	None	N
D/Y	0.2359	likely_benign	0.1843	benign	-0.288	Destabilizing	0.741	D	0.441	neutral	N	0.383502526	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.