TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8874	26845;26846;26847	chr2:178714038;178714037;178714036	chr2:179578765;179578764;179578763
N2AB	8557	25894;25895;25896	chr2:178714038;178714037;178714036	chr2:179578765;179578764;179578763
N2A	7630	23113;23114;23115	chr2:178714038;178714037;178714036	chr2:179578765;179578764;179578763
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-74
• Domain position: 45
• Structural Position: 111
• Q(SASA): 0.972
• 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/K	None	None	None	N	0.14	0.129	0.0716867268079	gnomAD-4.0.0	6.84312E-07	None	None	None	None	N	None	0	0	None	3.82819E-05	0	None	0	0	0	0	0
N/S	rs1222843561	0.441	None	N	0.084	0.105	0.0138822411134	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	0	0
N/S	rs1222843561	0.441	None	N	0.084	0.105	0.0138822411134	gnomAD-4.0.0	1.59169E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88345E-05	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	0.098	likely_benign	0.1186	benign	-0.05	Destabilizing	0.007	N	0.193	neutral	None	None	None	None	N
N/C	0.1655	likely_benign	0.1979	benign	0.168	Stabilizing	0.676	D	0.137	neutral	None	None	None	None	N
N/D	0.0869	likely_benign	0.0906	benign	0.175	Stabilizing	0.012	N	0.191	neutral	N	0.412108193	None	None	N
N/E	0.1634	likely_benign	0.1661	benign	0.114	Stabilizing	0.016	N	0.145	neutral	None	None	None	None	N
N/F	0.3135	likely_benign	0.3603	ambiguous	-0.668	Destabilizing	0.038	N	0.259	neutral	None	None	None	None	N
N/G	0.1222	likely_benign	0.1451	benign	-0.14	Destabilizing	0.016	N	0.153	neutral	None	None	None	None	N
N/H	0.0745	likely_benign	0.0735	benign	-0.144	Destabilizing	None	N	0.14	neutral	N	0.456112473	None	None	N
N/I	0.1254	likely_benign	0.1484	benign	0.086	Stabilizing	0.055	N	0.243	neutral	N	0.504847783	None	None	N
N/K	0.1177	likely_benign	0.1124	benign	0.172	Stabilizing	None	N	0.14	neutral	N	0.409550677	None	None	N
N/L	0.1331	likely_benign	0.1513	benign	0.086	Stabilizing	0.031	N	0.167	neutral	None	None	None	None	N
N/M	0.1944	likely_benign	0.2176	benign	0.115	Stabilizing	0.628	D	0.162	neutral	None	None	None	None	N
N/P	0.2116	likely_benign	0.2535	benign	0.064	Stabilizing	0.072	N	0.274	neutral	None	None	None	None	N
N/Q	0.1358	likely_benign	0.1332	benign	-0.188	Destabilizing	0.072	N	0.15	neutral	None	None	None	None	N
N/R	0.1255	likely_benign	0.1166	benign	0.238	Stabilizing	None	N	0.159	neutral	None	None	None	None	N
N/S	0.0563	likely_benign	0.0634	benign	0.009	Stabilizing	None	N	0.084	neutral	N	0.399448327	None	None	N
N/T	0.0757	likely_benign	0.0909	benign	0.062	Stabilizing	0.012	N	0.179	neutral	N	0.438084073	None	None	N
N/V	0.1285	likely_benign	0.1523	benign	0.064	Stabilizing	0.072	N	0.213	neutral	None	None	None	None	N
N/W	0.4736	ambiguous	0.4954	ambiguous	-0.814	Destabilizing	0.676	D	0.142	neutral	None	None	None	None	N
N/Y	0.1066	likely_benign	0.1156	benign	-0.474	Destabilizing	0.001	N	0.177	neutral	N	0.479989411	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.