TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22688	68287;68288;68289	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
N2AB	21047	63364;63365;63366	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
N2A	20120	60583;60584;60585	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
N2B	13623	41092;41093;41094	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
Novex-1	13748	41467;41468;41469	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
Novex-2	13815	41668;41669;41670	chr2:178578968;178578967;178578966	chr2:179443695;179443694;179443693
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: Fn3-52
• Domain position: 46
• Structural Position: 60
• Q(SASA): 0.4154
• 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/I	rs748527420	0.098	0.491	N	0.345	0.174	0.37762505005	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
N/I	rs748527420	0.098	0.491	N	0.345	0.174	0.37762505005	gnomAD-4.0.0	6.36947E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	5.73148E-05	0
N/K	None	None	0.166	N	0.175	0.098	0.143124449307	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	2.2876E-05	None	0	0	None	0	0	0	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	0.2373	likely_benign	0.1908	benign	-0.305	Destabilizing	0.007	N	0.127	neutral	None	None	None	None	N
N/C	0.2519	likely_benign	0.2199	benign	0.401	Stabilizing	0.965	D	0.312	neutral	None	None	None	None	N
N/D	0.2328	likely_benign	0.1922	benign	-0.038	Destabilizing	None	N	0.058	neutral	N	0.403019855	None	None	N
N/E	0.5415	ambiguous	0.4569	ambiguous	-0.079	Destabilizing	0.209	N	0.185	neutral	None	None	None	None	N
N/F	0.6309	likely_pathogenic	0.5284	ambiguous	-0.685	Destabilizing	0.901	D	0.372	neutral	None	None	None	None	N
N/G	0.2472	likely_benign	0.2158	benign	-0.474	Destabilizing	0.103	N	0.181	neutral	None	None	None	None	N
N/H	0.1056	likely_benign	0.0917	benign	-0.552	Destabilizing	0.873	D	0.19	neutral	N	0.443367755	None	None	N
N/I	0.418	ambiguous	0.3246	benign	0.053	Stabilizing	0.491	N	0.345	neutral	N	0.500261187	None	None	N
N/K	0.4215	ambiguous	0.3312	benign	0.056	Stabilizing	0.166	N	0.175	neutral	N	0.416661156	None	None	N
N/L	0.2888	likely_benign	0.2368	benign	0.053	Stabilizing	0.209	N	0.266	neutral	None	None	None	None	N
N/M	0.3792	ambiguous	0.3086	benign	0.438	Stabilizing	0.965	D	0.297	neutral	None	None	None	None	N
N/P	0.7522	likely_pathogenic	0.7102	pathogenic	-0.04	Destabilizing	0.722	D	0.279	neutral	None	None	None	None	N
N/Q	0.3635	ambiguous	0.2996	benign	-0.364	Destabilizing	0.561	D	0.154	neutral	None	None	None	None	N
N/R	0.4147	ambiguous	0.3343	benign	0.121	Stabilizing	0.004	N	0.121	neutral	None	None	None	None	N
N/S	0.0849	likely_benign	0.0767	benign	-0.097	Destabilizing	0.005	N	0.093	neutral	N	0.389031837	None	None	N
N/T	0.1166	likely_benign	0.0988	benign	-0.003	Destabilizing	0.002	N	0.062	neutral	N	0.376700045	None	None	N
N/V	0.3898	ambiguous	0.3085	benign	-0.04	Destabilizing	0.209	N	0.243	neutral	None	None	None	None	N
N/W	0.755	likely_pathogenic	0.7081	pathogenic	-0.684	Destabilizing	0.991	D	0.321	neutral	None	None	None	None	N
N/Y	0.2124	likely_benign	0.1717	benign	-0.419	Destabilizing	0.954	D	0.341	neutral	N	0.481675427	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.