TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22492	67699;67700;67701	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
N2AB	20851	62776;62777;62778	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
N2A	19924	59995;59996;59997	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
N2B	13427	40504;40505;40506	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
Novex-1	13552	40879;40880;40881	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
Novex-2	13619	41080;41081;41082	chr2:178579723;178579722;178579721	chr2:179444450;179444449;179444448
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: Fn3-51
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2219
• 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/N	rs1268182721	-0.665	0.029	N	0.324	0.049	0.177238962908	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
T/S	None	None	None	N	0.106	0.097	0.0884992946249	gnomAD-4.0.0	2.05322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69897E-06	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
T/A	0.1051	likely_benign	0.0984	benign	-0.94	Destabilizing	0.005	N	0.263	neutral	N	0.440674166	None	None	N
T/C	0.4463	ambiguous	0.4031	ambiguous	-0.501	Destabilizing	0.356	N	0.435	neutral	None	None	None	None	N
T/D	0.3147	likely_benign	0.2698	benign	-0.357	Destabilizing	0.016	N	0.398	neutral	None	None	None	None	N
T/E	0.3003	likely_benign	0.2678	benign	-0.286	Destabilizing	None	N	0.142	neutral	None	None	None	None	N
T/F	0.4067	ambiguous	0.3724	ambiguous	-0.73	Destabilizing	0.214	N	0.479	neutral	None	None	None	None	N
T/G	0.1779	likely_benign	0.1513	benign	-1.271	Destabilizing	0.016	N	0.371	neutral	None	None	None	None	N
T/H	0.3151	likely_benign	0.2798	benign	-1.46	Destabilizing	0.356	N	0.466	neutral	None	None	None	None	N
T/I	0.2897	likely_benign	0.2581	benign	-0.122	Destabilizing	None	N	0.178	neutral	N	0.457337129	None	None	N
T/K	0.1956	likely_benign	0.1808	benign	-0.754	Destabilizing	0.016	N	0.391	neutral	None	None	None	None	N
T/L	0.1135	likely_benign	0.106	benign	-0.122	Destabilizing	0.007	N	0.377	neutral	None	None	None	None	N
T/M	0.1089	likely_benign	0.1014	benign	0.036	Stabilizing	0.214	N	0.466	neutral	None	None	None	None	N
T/N	0.1109	likely_benign	0.0973	benign	-0.863	Destabilizing	0.029	N	0.324	neutral	N	0.428379659	None	None	N
T/P	0.1843	likely_benign	0.159	benign	-0.362	Destabilizing	0.055	N	0.45	neutral	N	0.430590458	None	None	N
T/Q	0.2266	likely_benign	0.2079	benign	-0.868	Destabilizing	0.072	N	0.403	neutral	None	None	None	None	N
T/R	0.1634	likely_benign	0.1577	benign	-0.67	Destabilizing	0.072	N	0.446	neutral	None	None	None	None	N
T/S	0.1022	likely_benign	0.0913	benign	-1.159	Destabilizing	None	N	0.106	neutral	N	0.436844427	None	None	N
T/V	0.1891	likely_benign	0.1728	benign	-0.362	Destabilizing	None	N	0.086	neutral	None	None	None	None	N
T/W	0.6617	likely_pathogenic	0.6273	pathogenic	-0.73	Destabilizing	0.864	D	0.443	neutral	None	None	None	None	N
T/Y	0.4128	ambiguous	0.3802	ambiguous	-0.48	Destabilizing	0.356	N	0.471	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.