TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15101	45526;45527;45528	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
N2AB	13460	40603;40604;40605	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
N2A	12533	37822;37823;37824	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
N2B	6036	18331;18332;18333	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
Novex-1	6161	18706;18707;18708	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
Novex-2	6228	18907;18908;18909	chr2:178621523;178621522;178621521	chr2:179486250;179486249;179486248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-102
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1522
• 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
N/H	rs879050695	None	0.009	N	0.432	0.314	None	gnomAD-4.0.0	3.42364E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49981E-06	0	0
N/K	None	None	0.379	N	0.651	0.377	0.256793551483	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
N/S	None	None	0.016	N	0.242	0.229	0.143124449307	gnomAD-4.0.0	6.8472E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99947E-07	0	0
N/T	None	None	0.007	N	0.237	0.177	0.212008924253	gnomAD-4.0.0	6.8472E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99947E-07	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
N/A	0.2527	likely_benign	0.2577	benign	-1.895	Destabilizing	0.25	N	0.657	neutral	None	None	None	None	N
N/C	0.2233	likely_benign	0.2729	benign	-1.034	Destabilizing	0.992	D	0.769	deleterious	None	None	None	None	N
N/D	0.2795	likely_benign	0.2181	benign	-2.137	Highly Destabilizing	0.549	D	0.627	neutral	D	0.529115875	None	None	N
N/E	0.5821	likely_pathogenic	0.5199	ambiguous	-1.857	Destabilizing	0.617	D	0.644	neutral	None	None	None	None	N
N/F	0.4246	ambiguous	0.4562	ambiguous	-1.314	Destabilizing	0.92	D	0.805	deleterious	None	None	None	None	N
N/G	0.4135	ambiguous	0.4175	ambiguous	-2.276	Highly Destabilizing	0.25	N	0.607	neutral	None	None	None	None	N
N/H	0.0946	likely_benign	0.1014	benign	-1.435	Destabilizing	0.009	N	0.432	neutral	N	0.469611201	None	None	N
N/I	0.1836	likely_benign	0.1797	benign	-0.841	Destabilizing	0.81	D	0.792	deleterious	N	0.465068084	None	None	N
N/K	0.5189	ambiguous	0.4595	ambiguous	-0.471	Destabilizing	0.379	N	0.651	neutral	N	0.42959675	None	None	N
N/L	0.2756	likely_benign	0.2693	benign	-0.841	Destabilizing	0.447	N	0.75	deleterious	None	None	None	None	N
N/M	0.3755	ambiguous	0.3922	ambiguous	-0.703	Destabilizing	0.992	D	0.743	deleterious	None	None	None	None	N
N/P	0.9715	likely_pathogenic	0.9581	pathogenic	-1.172	Destabilizing	0.92	D	0.767	deleterious	None	None	None	None	N
N/Q	0.4121	ambiguous	0.4031	ambiguous	-1.047	Destabilizing	0.85	D	0.7	prob.neutral	None	None	None	None	N
N/R	0.4347	ambiguous	0.4046	ambiguous	-0.555	Destabilizing	0.617	D	0.667	neutral	None	None	None	None	N
N/S	0.0712	likely_benign	0.0737	benign	-1.61	Destabilizing	0.016	N	0.242	neutral	N	0.30086263	None	None	N
N/T	0.1199	likely_benign	0.1231	benign	-1.149	Destabilizing	0.007	N	0.237	neutral	N	0.27285123	None	None	N
N/V	0.2107	likely_benign	0.2213	benign	-1.172	Destabilizing	0.447	N	0.753	deleterious	None	None	None	None	N
N/W	0.793	likely_pathogenic	0.8129	pathogenic	-1.129	Destabilizing	0.992	D	0.785	deleterious	None	None	None	None	N
N/Y	0.1532	likely_benign	0.1663	benign	-0.867	Destabilizing	0.81	D	0.766	deleterious	N	0.467043292	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.