TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6919	20980;20981;20982	chr2:178725449;178725448;178725447	chr2:179590176;179590175;179590174
N2AB	6602	20029;20030;20031	chr2:178725449;178725448;178725447	chr2:179590176;179590175;179590174
N2A	5675	17248;17249;17250	chr2:178725449;178725448;178725447	chr2:179590176;179590175;179590174
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-53
• Domain position: 66
• Structural Position: 146
• Q(SASA): 0.5713
• 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
P/L	None	None	0.001	N	0.145	0.134	0.178374595973	gnomAD-4.0.0	1.59365E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43674E-05	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
P/A	0.0729	likely_benign	0.0695	benign	-0.505	Destabilizing	0.021	N	0.189	neutral	N	0.441855097	None	None	N
P/C	0.6	likely_pathogenic	0.5607	ambiguous	-0.533	Destabilizing	0.94	D	0.296	neutral	None	None	None	None	N
P/D	0.4021	ambiguous	0.3828	ambiguous	-0.532	Destabilizing	0.418	N	0.274	neutral	None	None	None	None	N
P/E	0.2562	likely_benign	0.2438	benign	-0.664	Destabilizing	0.228	N	0.26	neutral	None	None	None	None	N
P/F	0.3861	ambiguous	0.3614	ambiguous	-0.844	Destabilizing	0.418	N	0.38	neutral	None	None	None	None	N
P/G	0.2513	likely_benign	0.2338	benign	-0.621	Destabilizing	0.129	N	0.238	neutral	None	None	None	None	N
P/H	0.2151	likely_benign	0.2098	benign	-0.265	Destabilizing	0.836	D	0.282	neutral	None	None	None	None	N
P/I	0.2082	likely_benign	0.2052	benign	-0.353	Destabilizing	0.001	N	0.181	neutral	None	None	None	None	N
P/K	0.2394	likely_benign	0.237	benign	-0.476	Destabilizing	0.129	N	0.259	neutral	None	None	None	None	N
P/L	0.0918	likely_benign	0.0908	benign	-0.353	Destabilizing	0.001	N	0.145	neutral	N	0.47771711	None	None	N
P/M	0.2243	likely_benign	0.2153	benign	-0.313	Destabilizing	0.716	D	0.345	neutral	None	None	None	None	N
P/N	0.2679	likely_benign	0.2644	benign	-0.146	Destabilizing	0.264	N	0.335	neutral	None	None	None	None	N
P/Q	0.163	likely_benign	0.1565	benign	-0.444	Destabilizing	0.351	N	0.311	neutral	N	0.452818505	None	None	N
P/R	0.1812	likely_benign	0.1797	benign	0.086	Stabilizing	0.351	N	0.361	neutral	N	0.45587947	None	None	N
P/S	0.1209	likely_benign	0.1163	benign	-0.447	Destabilizing	0.001	N	0.115	neutral	N	0.479450693	None	None	N
P/T	0.0869	likely_benign	0.0871	benign	-0.488	Destabilizing	0.003	N	0.125	neutral	N	0.513120549	None	None	N
P/V	0.1518	likely_benign	0.1467	benign	-0.37	Destabilizing	0.001	N	0.105	neutral	None	None	None	None	N
P/W	0.5956	likely_pathogenic	0.5736	pathogenic	-0.917	Destabilizing	0.983	D	0.291	neutral	None	None	None	None	N
P/Y	0.3789	ambiguous	0.3616	ambiguous	-0.614	Destabilizing	0.94	D	0.399	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.