TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9943	30052;30053;30054	chr2:178704645;178704644;178704643	chr2:179569372;179569371;179569370
N2AB	9626	29101;29102;29103	chr2:178704645;178704644;178704643	chr2:179569372;179569371;179569370
N2A	8699	26320;26321;26322	chr2:178704645;178704644;178704643	chr2:179569372;179569371;179569370
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: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-84
• Domain position: 44
• Structural Position: 70
• Q(SASA): 0.4198
• 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	0.042	None	0.333	0.13	0.428976297845	gnomAD-4.0.0	1.59486E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43649E-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	0.084	likely_benign	0.0973	benign	-0.429	Destabilizing	0.019	N	0.194	neutral	None	None	None	None	N
P/C	0.7089	likely_pathogenic	0.7797	pathogenic	-0.696	Destabilizing	0.883	D	0.379	neutral	None	None	None	None	N
P/D	0.4779	ambiguous	0.5052	ambiguous	-0.261	Destabilizing	0.104	N	0.311	neutral	None	None	None	None	N
P/E	0.3139	likely_benign	0.3547	ambiguous	-0.371	Destabilizing	0.055	N	0.298	neutral	None	None	None	None	N
P/F	0.6643	likely_pathogenic	0.743	pathogenic	-0.663	Destabilizing	0.001	N	0.267	neutral	None	None	None	None	N
P/G	0.3914	ambiguous	0.4568	ambiguous	-0.55	Destabilizing	0.055	N	0.291	neutral	None	None	None	None	N
P/H	0.2417	likely_benign	0.3144	benign	-0.131	Destabilizing	0.602	D	0.385	neutral	None	None	None	None	N
P/I	0.3979	ambiguous	0.4944	ambiguous	-0.261	Destabilizing	0.22	N	0.427	neutral	None	None	None	None	N
P/K	0.2458	likely_benign	0.3309	benign	-0.452	Destabilizing	0.055	N	0.304	neutral	None	None	None	None	N
P/L	0.1758	likely_benign	0.218	benign	-0.261	Destabilizing	0.042	N	0.333	neutral	None	None	None	None	N
P/M	0.4389	ambiguous	0.5296	ambiguous	-0.404	Destabilizing	0.667	D	0.383	neutral	None	None	None	None	N
P/N	0.3485	ambiguous	0.4174	ambiguous	-0.234	Destabilizing	0.124	N	0.344	neutral	None	None	None	None	N
P/Q	0.1776	likely_benign	0.2356	benign	-0.45	Destabilizing	0.22	N	0.383	neutral	None	None	None	None	N
P/R	0.1758	likely_benign	0.248	benign	0.035	Stabilizing	0.001	N	0.23	neutral	None	None	None	None	N
P/S	0.1494	likely_benign	0.1795	benign	-0.582	Destabilizing	None	N	0.11	neutral	None	None	None	None	N
P/T	0.1221	likely_benign	0.1502	benign	-0.589	Destabilizing	0.042	N	0.295	neutral	None	None	None	None	N
P/V	0.2698	likely_benign	0.3302	benign	-0.283	Destabilizing	0.22	N	0.344	neutral	None	None	None	None	N
P/W	0.8113	likely_pathogenic	0.8608	pathogenic	-0.749	Destabilizing	0.958	D	0.388	neutral	None	None	None	None	N
P/Y	0.5425	ambiguous	0.6468	pathogenic	-0.453	Destabilizing	0.124	N	0.466	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.