TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21739	65440;65441;65442	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
N2AB	20098	60517;60518;60519	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
N2A	19171	57736;57737;57738	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
N2B	12674	38245;38246;38247	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
Novex-1	12799	38620;38621;38622	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
Novex-2	12866	38821;38822;38823	chr2:178584336;178584335;178584334	chr2:179449063;179449062;179449061
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-45
• Domain position: 81
• Structural Position: 113
• Q(SASA): 0.7493
• Predicted PPI site: I

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
K/N	rs1457832691	0.236	0.324	N	0.34	0.12	0.204665344411	gnomAD-2.1.1	4.06E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
K/N	rs1457832691	0.236	0.324	N	0.34	0.12	0.204665344411	gnomAD-4.0.0	1.60857E-06	None	None	None	None	I	None	0	2.29495E-05	None	0	0	None	0	0	0	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
K/A	0.5199	ambiguous	0.4357	ambiguous	0.049	Stabilizing	0.207	N	0.456	neutral	None	None	None	None	I
K/C	0.8624	likely_pathogenic	0.7816	pathogenic	-0.235	Destabilizing	0.981	D	0.439	neutral	None	None	None	None	I
K/D	0.8045	likely_pathogenic	0.7439	pathogenic	-0.018	Destabilizing	0.388	N	0.464	neutral	None	None	None	None	I
K/E	0.3315	likely_benign	0.282	benign	-0.015	Destabilizing	0.09	N	0.367	neutral	N	0.448234857	None	None	I
K/F	0.9099	likely_pathogenic	0.8661	pathogenic	-0.209	Destabilizing	0.69	D	0.495	neutral	None	None	None	None	I
K/G	0.7173	likely_pathogenic	0.6339	pathogenic	-0.129	Destabilizing	0.388	N	0.537	neutral	None	None	None	None	I
K/H	0.4969	ambiguous	0.4128	ambiguous	-0.361	Destabilizing	0.818	D	0.409	neutral	None	None	None	None	I
K/I	0.5236	ambiguous	0.4475	ambiguous	0.437	Stabilizing	0.193	N	0.529	neutral	N	0.440367522	None	None	I
K/L	0.4411	ambiguous	0.3557	ambiguous	0.437	Stabilizing	0.002	N	0.253	neutral	None	None	None	None	I
K/M	0.3563	ambiguous	0.3015	benign	0.153	Stabilizing	0.054	N	0.401	neutral	None	None	None	None	I
K/N	0.6697	likely_pathogenic	0.6059	pathogenic	0.194	Stabilizing	0.324	N	0.34	neutral	N	0.491409631	None	None	I
K/P	0.8381	likely_pathogenic	0.7726	pathogenic	0.335	Stabilizing	0.818	D	0.442	neutral	None	None	None	None	I
K/Q	0.2066	likely_benign	0.1743	benign	0.047	Stabilizing	0.018	N	0.294	neutral	N	0.436999143	None	None	I
K/R	0.0818	likely_benign	0.0752	benign	-0.029	Destabilizing	0.001	N	0.125	neutral	N	0.429630453	None	None	I
K/S	0.6589	likely_pathogenic	0.5796	pathogenic	-0.24	Destabilizing	0.388	N	0.317	neutral	None	None	None	None	I
K/T	0.3572	ambiguous	0.3031	benign	-0.096	Destabilizing	0.324	N	0.493	neutral	N	0.453448675	None	None	I
K/V	0.4743	ambiguous	0.3958	ambiguous	0.335	Stabilizing	0.241	N	0.519	neutral	None	None	None	None	I
K/W	0.9012	likely_pathogenic	0.8513	pathogenic	-0.269	Destabilizing	0.981	D	0.465	neutral	None	None	None	None	I
K/Y	0.7965	likely_pathogenic	0.7193	pathogenic	0.093	Stabilizing	0.818	D	0.499	neutral	None	None	None	None	I

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.