TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26961	81106;81107;81108	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
N2AB	25320	76183;76184;76185	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
N2A	24393	73402;73403;73404	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
N2B	17896	53911;53912;53913	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
Novex-1	18021	54286;54287;54288	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
Novex-2	18088	54487;54488;54489	chr2:178565251;178565250;178565249	chr2:179429978;179429977;179429976
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: Ig-139
• Domain position: 82
• Structural Position: 166
• Q(SASA): 0.1867
• 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/E	rs749194310	-0.553	0.193	N	0.665	0.181	0.365703291355	gnomAD-2.1.1	8.06E-06	None	None	None	None	N	None	6.47E-05	2.9E-05	None	0	0	None	0	None	0	0	0
A/E	rs749194310	-0.553	0.193	N	0.665	0.181	0.365703291355	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/E	rs749194310	-0.553	0.193	N	0.665	0.181	0.365703291355	gnomAD-4.0.0	2.47909E-06	None	None	None	None	N	None	2.67023E-05	1.66778E-05	None	0	0	None	0	0	8.47679E-07	0	0
A/T	rs779484612	-0.634	0.001	N	0.218	0.116	0.209622950755	gnomAD-2.1.1	2.42E-05	None	None	None	None	N	None	6.46E-05	1.45003E-04	None	0	0	None	0	None	0	0	0
A/T	rs779484612	-0.634	0.001	N	0.218	0.116	0.209622950755	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/T	rs779484612	-0.634	0.001	N	0.218	0.116	0.209622950755	gnomAD-4.0.0	6.19765E-06	None	None	None	None	N	None	2.67023E-05	1.16744E-04	None	0	0	None	0	1.64528E-04	0	0	0
A/V	rs749194310	-0.171	0.003	N	0.217	0.102	0.293147016451	gnomAD-2.1.1	6.44E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.41161E-04	0
A/V	rs749194310	-0.171	0.003	N	0.217	0.102	0.293147016451	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	4.41E-05	0	4.78469E-04
A/V	rs749194310	-0.171	0.003	N	0.217	0.102	0.293147016451	gnomAD-4.0.0	2.31795E-04	None	None	None	None	N	None	1.33511E-05	0	None	0	0	None	0	0	3.13641E-04	0	4.80384E-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
A/C	0.4196	ambiguous	0.4071	ambiguous	-0.938	Destabilizing	0.944	D	0.699	prob.neutral	None	None	None	None	N
A/D	0.3254	likely_benign	0.3042	benign	-1.021	Destabilizing	0.69	D	0.747	deleterious	None	None	None	None	N
A/E	0.2768	likely_benign	0.2502	benign	-1.133	Destabilizing	0.193	N	0.665	neutral	N	0.51583922	None	None	N
A/F	0.3447	ambiguous	0.3122	benign	-1.255	Destabilizing	0.818	D	0.759	deleterious	None	None	None	None	N
A/G	0.2205	likely_benign	0.2092	benign	-0.941	Destabilizing	0.324	N	0.622	neutral	N	0.509992464	None	None	N
A/H	0.4841	ambiguous	0.4497	ambiguous	-0.949	Destabilizing	0.944	D	0.707	prob.neutral	None	None	None	None	N
A/I	0.1597	likely_benign	0.1388	benign	-0.619	Destabilizing	0.241	N	0.669	neutral	None	None	None	None	N
A/K	0.4093	ambiguous	0.3674	ambiguous	-0.931	Destabilizing	0.002	N	0.351	neutral	None	None	None	None	N
A/L	0.1879	likely_benign	0.1611	benign	-0.619	Destabilizing	0.116	N	0.631	neutral	None	None	None	None	N
A/M	0.1917	likely_benign	0.1637	benign	-0.465	Destabilizing	0.818	D	0.721	prob.delet.	None	None	None	None	N
A/N	0.3003	likely_benign	0.2612	benign	-0.638	Destabilizing	0.69	D	0.755	deleterious	None	None	None	None	N
A/P	0.9548	likely_pathogenic	0.9431	pathogenic	-0.646	Destabilizing	0.773	D	0.759	deleterious	N	0.515018894	None	None	N
A/Q	0.3445	ambiguous	0.3158	benign	-0.95	Destabilizing	0.69	D	0.751	deleterious	None	None	None	None	N
A/R	0.3837	ambiguous	0.3582	ambiguous	-0.472	Destabilizing	0.241	N	0.744	deleterious	None	None	None	None	N
A/S	0.102	likely_benign	0.0991	benign	-0.916	Destabilizing	0.09	N	0.591	neutral	N	0.518514166	None	None	N
A/T	0.0709	likely_benign	0.0687	benign	-0.954	Destabilizing	0.001	N	0.218	neutral	N	0.491194279	None	None	N
A/V	0.0869	likely_benign	0.0786	benign	-0.646	Destabilizing	0.003	N	0.217	neutral	N	0.482822725	None	None	N
A/W	0.7966	likely_pathogenic	0.7796	pathogenic	-1.404	Destabilizing	0.981	D	0.756	deleterious	None	None	None	None	N
A/Y	0.4971	ambiguous	0.4574	ambiguous	-1.049	Destabilizing	0.818	D	0.757	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.