TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29161	87706;87707;87708	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
N2AB	27520	82783;82784;82785	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
N2A	26593	80002;80003;80004	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
N2B	20096	60511;60512;60513	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
Novex-1	20221	60886;60887;60888	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
Novex-2	20288	61087;61088;61089	chr2:178557873;178557872;178557871	chr2:179422600;179422599;179422598
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: Fn3-100
• Domain position: 25
• Structural Position: 26
• Q(SASA): 0.4482
• 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/A	None	None	0.767	N	0.374	0.335	0.283761946502	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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	0.0706	likely_benign	0.0745	benign	-1.667	Destabilizing	0.767	D	0.374	neutral	N	0.503418923	None	None	N
P/C	0.4813	ambiguous	0.5304	ambiguous	-1.129	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
P/D	0.6973	likely_pathogenic	0.6809	pathogenic	-1.734	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/E	0.3598	ambiguous	0.3765	ambiguous	-1.664	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/F	0.556	ambiguous	0.586	pathogenic	-1.177	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/G	0.4134	ambiguous	0.424	ambiguous	-2.05	Highly Destabilizing	0.997	D	0.741	deleterious	None	None	None	None	N
P/H	0.3117	likely_benign	0.3357	benign	-1.568	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/I	0.2489	likely_benign	0.2798	benign	-0.68	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
P/K	0.318	likely_benign	0.3567	ambiguous	-1.493	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/L	0.1096	likely_benign	0.1226	benign	-0.68	Destabilizing	0.999	D	0.83	deleterious	N	0.51995492	None	None	N
P/M	0.2287	likely_benign	0.2549	benign	-0.561	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
P/N	0.4558	ambiguous	0.4537	ambiguous	-1.403	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/Q	0.1804	likely_benign	0.1977	benign	-1.472	Destabilizing	1.0	D	0.853	deleterious	N	0.496508294	None	None	N
P/R	0.2672	likely_benign	0.3147	benign	-1.032	Destabilizing	0.999	D	0.863	deleterious	N	0.494520058	None	None	N
P/S	0.1692	likely_benign	0.1699	benign	-1.925	Destabilizing	0.998	D	0.745	deleterious	N	0.495747826	None	None	N
P/T	0.1363	likely_benign	0.1456	benign	-1.729	Destabilizing	0.999	D	0.775	deleterious	N	0.509990967	None	None	N
P/V	0.1787	likely_benign	0.1983	benign	-0.976	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
P/W	0.8031	likely_pathogenic	0.8313	pathogenic	-1.447	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/Y	0.5416	ambiguous	0.5873	pathogenic	-1.134	Destabilizing	1.0	D	0.882	deleterious	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.