TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14543	43852;43853;43854	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
N2AB	12902	38929;38930;38931	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
N2A	11975	36148;36149;36150	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
N2B	5478	16657;16658;16659	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
Novex-1	5603	17032;17033;17034	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
Novex-2	5670	17233;17234;17235	chr2:178632267;178632266;178632265	chr2:179496994;179496993;179496992
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-96
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.2639
• 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
S/A	None	None	0.052	N	0.39	0.234	0.247322355667	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
S/A	0.0939	likely_benign	0.0867	benign	-0.808	Destabilizing	0.052	N	0.39	neutral	N	0.49177538	None	None	N
S/C	0.1334	likely_benign	0.1429	benign	-0.793	Destabilizing	0.935	D	0.449	neutral	None	None	None	None	N
S/D	0.3353	likely_benign	0.31	benign	-0.993	Destabilizing	0.262	N	0.399	neutral	None	None	None	None	N
S/E	0.3976	ambiguous	0.3715	ambiguous	-0.98	Destabilizing	0.149	N	0.37	neutral	None	None	None	None	N
S/F	0.105	likely_benign	0.121	benign	-1.146	Destabilizing	0.235	N	0.45	neutral	None	None	None	None	N
S/G	0.1428	likely_benign	0.1316	benign	-1.037	Destabilizing	0.067	N	0.373	neutral	None	None	None	None	N
S/H	0.23	likely_benign	0.242	benign	-1.561	Destabilizing	0.001	N	0.16	neutral	None	None	None	None	N
S/I	0.1258	likely_benign	0.1243	benign	-0.301	Destabilizing	0.081	N	0.418	neutral	None	None	None	None	N
S/K	0.5227	ambiguous	0.4841	ambiguous	-0.706	Destabilizing	0.149	N	0.363	neutral	None	None	None	None	N
S/L	0.0901	likely_benign	0.0944	benign	-0.301	Destabilizing	None	N	0.243	neutral	N	0.405864265	None	None	N
S/M	0.2079	likely_benign	0.211	benign	0.038	Stabilizing	0.38	N	0.463	neutral	None	None	None	None	N
S/N	0.1478	likely_benign	0.1352	benign	-0.843	Destabilizing	0.149	N	0.374	neutral	None	None	None	None	N
S/P	0.689	likely_pathogenic	0.7478	pathogenic	-0.438	Destabilizing	0.741	D	0.447	neutral	N	0.513518936	None	None	N
S/Q	0.4227	ambiguous	0.4039	ambiguous	-1.078	Destabilizing	0.555	D	0.451	neutral	None	None	None	None	N
S/R	0.4044	ambiguous	0.37	ambiguous	-0.568	Destabilizing	0.38	N	0.449	neutral	None	None	None	None	N
S/T	0.0868	likely_benign	0.0827	benign	-0.783	Destabilizing	0.211	N	0.408	neutral	N	0.49237478	None	None	N
S/V	0.161	likely_benign	0.1595	benign	-0.438	Destabilizing	0.081	N	0.419	neutral	None	None	None	None	N
S/W	0.1335	likely_benign	0.2123	benign	-1.134	Destabilizing	0.001	N	0.386	neutral	None	None	None	None	N
S/Y	0.1056	likely_benign	0.1163	benign	-0.821	Destabilizing	0.081	N	0.419	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.