TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22595	68008;68009;68010	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
N2AB	20954	63085;63086;63087	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
N2A	20027	60304;60305;60306	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
N2B	13530	40813;40814;40815	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
Novex-1	13655	41188;41189;41190	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
Novex-2	13722	41389;41390;41391	chr2:178579247;178579246;178579245	chr2:179443974;179443973;179443972
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-127
• Domain position: 36
• Structural Position: 102
• Q(SASA): 0.8793
• 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	rs1438797997	-0.028	0.003	N	0.297	0.091	0.104622674875	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
T/A	rs1438797997	-0.028	0.003	N	0.297	0.091	0.104622674875	gnomAD-4.0.0	4.33886E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.08668E-06	0	1.60154E-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	0.0711	likely_benign	0.0808	benign	-0.178	Destabilizing	0.003	N	0.297	neutral	N	0.426712286	None	None	N
T/C	0.3947	ambiguous	0.4284	ambiguous	-0.369	Destabilizing	0.973	D	0.477	neutral	None	None	None	None	N
T/D	0.2721	likely_benign	0.3029	benign	0.138	Stabilizing	0.826	D	0.403	neutral	None	None	None	None	N
T/E	0.2342	likely_benign	0.2591	benign	0.051	Stabilizing	0.404	N	0.387	neutral	None	None	None	None	N
T/F	0.2811	likely_benign	0.3354	benign	-0.851	Destabilizing	0.906	D	0.513	neutral	None	None	None	None	N
T/G	0.1445	likely_benign	0.1609	benign	-0.24	Destabilizing	0.404	N	0.438	neutral	None	None	None	None	N
T/H	0.2187	likely_benign	0.244	benign	-0.398	Destabilizing	0.973	D	0.506	neutral	None	None	None	None	N
T/I	0.2065	likely_benign	0.2517	benign	-0.14	Destabilizing	0.782	D	0.419	neutral	N	0.500017966	None	None	N
T/K	0.1584	likely_benign	0.1707	benign	-0.231	Destabilizing	0.404	N	0.391	neutral	None	None	None	None	N
T/L	0.1164	likely_benign	0.1361	benign	-0.14	Destabilizing	0.404	N	0.389	neutral	None	None	None	None	N
T/M	0.1024	likely_benign	0.1137	benign	-0.178	Destabilizing	0.991	D	0.421	neutral	None	None	None	None	N
T/N	0.1028	likely_benign	0.1165	benign	-0.079	Destabilizing	0.782	D	0.386	neutral	N	0.44448997	None	None	N
T/P	0.1041	likely_benign	0.1188	benign	-0.128	Destabilizing	0.879	D	0.415	neutral	N	0.430232594	None	None	N
T/Q	0.1799	likely_benign	0.1914	benign	-0.258	Destabilizing	0.826	D	0.413	neutral	None	None	None	None	N
T/R	0.1571	likely_benign	0.1675	benign	0.036	Stabilizing	0.004	N	0.326	neutral	None	None	None	None	N
T/S	0.0835	likely_benign	0.0933	benign	-0.252	Destabilizing	0.338	N	0.43	neutral	N	0.423613266	None	None	N
T/V	0.1478	likely_benign	0.1816	benign	-0.128	Destabilizing	0.404	N	0.385	neutral	None	None	None	None	N
T/W	0.6151	likely_pathogenic	0.6382	pathogenic	-0.942	Destabilizing	0.991	D	0.604	neutral	None	None	None	None	N
T/Y	0.2946	likely_benign	0.3256	benign	-0.611	Destabilizing	0.906	D	0.509	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.