TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18042	54349;54350;54351	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
N2AB	16401	49426;49427;49428	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
N2A	15474	46645;46646;46647	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
N2B	8977	27154;27155;27156	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
Novex-1	9102	27529;27530;27531	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
Novex-2	9169	27730;27731;27732	chr2:178605053;178605052;178605051	chr2:179469780;179469779;179469778
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-114
• Domain position: 75
• Structural Position: 153
• Q(SASA): 0.3248
• 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
T/A	rs1034402778	None	0.911	N	0.389	0.128	0.270889551736	gnomAD-4.0.0	3.42447E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.60064E-06	0	1.65865E-05

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
T/A	0.0963	likely_benign	0.1	benign	-0.852	Destabilizing	0.911	D	0.389	neutral	N	0.501061769	None	None	N
T/C	0.3607	ambiguous	0.3844	ambiguous	-0.616	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	N
T/D	0.4124	ambiguous	0.4338	ambiguous	-1.509	Destabilizing	0.985	D	0.573	neutral	None	None	None	None	N
T/E	0.3604	ambiguous	0.3756	ambiguous	-1.422	Destabilizing	0.985	D	0.571	neutral	None	None	None	None	N
T/F	0.1789	likely_benign	0.2022	benign	-0.77	Destabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
T/G	0.3118	likely_benign	0.325	benign	-1.187	Destabilizing	0.985	D	0.615	neutral	None	None	None	None	N
T/H	0.2398	likely_benign	0.263	benign	-1.567	Destabilizing	1.0	D	0.673	neutral	None	None	None	None	N
T/I	0.0947	likely_benign	0.1055	benign	-0.019	Destabilizing	0.961	D	0.55	neutral	N	0.476723472	None	None	N
T/K	0.2337	likely_benign	0.2533	benign	-0.87	Destabilizing	0.985	D	0.567	neutral	None	None	None	None	N
T/L	0.0822	likely_benign	0.089	benign	-0.019	Destabilizing	0.931	D	0.584	neutral	None	None	None	None	N
T/M	0.0842	likely_benign	0.0843	benign	0.33	Stabilizing	0.998	D	0.651	neutral	None	None	None	None	N
T/N	0.107	likely_benign	0.1131	benign	-1.271	Destabilizing	0.98	D	0.537	neutral	N	0.465314399	None	None	N
T/P	0.217	likely_benign	0.225	benign	-0.264	Destabilizing	0.997	D	0.609	neutral	D	0.523861271	None	None	N
T/Q	0.2341	likely_benign	0.247	benign	-1.29	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
T/R	0.2156	likely_benign	0.2223	benign	-0.807	Destabilizing	0.998	D	0.643	neutral	None	None	None	None	N
T/S	0.1187	likely_benign	0.121	benign	-1.353	Destabilizing	0.449	N	0.181	neutral	N	0.474317885	None	None	N
T/V	0.0909	likely_benign	0.0986	benign	-0.264	Destabilizing	0.469	N	0.213	neutral	None	None	None	None	N
T/W	0.5043	ambiguous	0.5118	ambiguous	-0.9	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
T/Y	0.2104	likely_benign	0.2253	benign	-0.572	Destabilizing	0.999	D	0.686	prob.neutral	None	None	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.