TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22510	67753;67754;67755	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
N2AB	20869	62830;62831;62832	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
N2A	19942	60049;60050;60051	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
N2B	13445	40558;40559;40560	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
Novex-1	13570	40933;40934;40935	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
Novex-2	13637	41134;41135;41136	chr2:178579669;178579668;178579667	chr2:179444396;179444395;179444394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-51
• Domain position: 60
• Structural Position: 93
• Q(SASA): 0.146
• 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
A/T	rs1394859997	-1.295	None	N	0.193	0.113	0.0920862733494	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	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
A/C	0.2775	likely_benign	0.2567	benign	-0.899	Destabilizing	0.356	N	0.636	neutral	None	None	None	None	N
A/D	0.4974	ambiguous	0.5416	ambiguous	-0.23	Destabilizing	0.072	N	0.733	prob.delet.	None	None	None	None	N
A/E	0.3337	likely_benign	0.3779	ambiguous	-0.252	Destabilizing	0.055	N	0.658	neutral	N	0.482965353	None	None	N
A/F	0.3085	likely_benign	0.2968	benign	-0.857	Destabilizing	0.072	N	0.73	prob.delet.	None	None	None	None	N
A/G	0.1713	likely_benign	0.1723	benign	-0.974	Destabilizing	0.024	N	0.562	neutral	N	0.471355558	None	None	N
A/H	0.4897	ambiguous	0.5059	ambiguous	-1.028	Destabilizing	0.628	D	0.773	deleterious	None	None	None	None	N
A/I	0.1591	likely_benign	0.1505	benign	-0.185	Destabilizing	None	N	0.434	neutral	None	None	None	None	N
A/K	0.4148	ambiguous	0.4667	ambiguous	-0.749	Destabilizing	0.031	N	0.649	neutral	None	None	None	None	N
A/L	0.1447	likely_benign	0.1369	benign	-0.185	Destabilizing	0.001	N	0.488	neutral	None	None	None	None	N
A/M	0.157	likely_benign	0.1573	benign	-0.318	Destabilizing	None	N	0.455	neutral	None	None	None	None	N
A/N	0.3541	ambiguous	0.4005	ambiguous	-0.503	Destabilizing	0.072	N	0.741	deleterious	None	None	None	None	N
A/P	0.5088	ambiguous	0.5331	ambiguous	-0.321	Destabilizing	0.106	N	0.696	prob.neutral	N	0.515825286	None	None	N
A/Q	0.3503	ambiguous	0.3725	ambiguous	-0.585	Destabilizing	0.136	N	0.715	prob.delet.	None	None	None	None	N
A/R	0.3694	ambiguous	0.4107	ambiguous	-0.538	Destabilizing	0.072	N	0.701	prob.neutral	None	None	None	None	N
A/S	0.1133	likely_benign	0.1183	benign	-0.98	Destabilizing	0.012	N	0.443	neutral	N	0.515305211	None	None	N
A/T	0.0737	likely_benign	0.0799	benign	-0.877	Destabilizing	None	N	0.193	neutral	N	0.493660502	None	None	N
A/V	0.0893	likely_benign	0.083	benign	-0.321	Destabilizing	None	N	0.197	neutral	N	0.36640012	None	None	N
A/W	0.6467	likely_pathogenic	0.6619	pathogenic	-1.126	Destabilizing	0.864	D	0.787	deleterious	None	None	None	None	N
A/Y	0.4333	ambiguous	0.4427	ambiguous	-0.708	Destabilizing	0.136	N	0.772	deleterious	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.