TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22757	68494;68495;68496	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
N2AB	21116	63571;63572;63573	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
N2A	20189	60790;60791;60792	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
N2B	13692	41299;41300;41301	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
Novex-1	13817	41674;41675;41676	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
Novex-2	13884	41875;41876;41877	chr2:178578671;178578670;178578669	chr2:179443398;179443397;179443396
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-53
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.4481
• 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
H/N	None	None	0.722	N	0.469	0.2	0.191931220699	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
H/A	0.3788	ambiguous	0.4282	ambiguous	-0.363	Destabilizing	0.775	D	0.574	neutral	None	None	None	None	N
H/C	0.1902	likely_benign	0.2278	benign	0.301	Stabilizing	0.996	D	0.76	deleterious	None	None	None	None	N
H/D	0.5314	ambiguous	0.5445	ambiguous	-0.182	Destabilizing	0.901	D	0.495	neutral	N	0.386780966	None	None	N
H/E	0.4984	ambiguous	0.5381	ambiguous	-0.16	Destabilizing	0.775	D	0.427	neutral	None	None	None	None	N
H/F	0.4634	ambiguous	0.5171	ambiguous	-0.032	Destabilizing	0.987	D	0.525	neutral	None	None	None	None	N
H/G	0.386	ambiguous	0.4271	ambiguous	-0.639	Destabilizing	0.775	D	0.573	neutral	None	None	None	None	N
H/I	0.6061	likely_pathogenic	0.6563	pathogenic	0.35	Stabilizing	0.961	D	0.705	prob.neutral	None	None	None	None	N
H/K	0.244	likely_benign	0.2738	benign	-0.327	Destabilizing	0.633	D	0.504	neutral	None	None	None	None	N
H/L	0.228	likely_benign	0.2623	benign	0.35	Stabilizing	0.901	D	0.634	neutral	N	0.479653842	None	None	N
H/M	0.6133	likely_pathogenic	0.6735	pathogenic	0.372	Stabilizing	0.996	D	0.669	neutral	None	None	None	None	N
H/N	0.199	likely_benign	0.2044	benign	-0.086	Destabilizing	0.722	D	0.469	neutral	N	0.399787549	None	None	N
H/P	0.327	likely_benign	0.3612	ambiguous	0.136	Stabilizing	0.949	D	0.667	neutral	N	0.418487953	None	None	N
H/Q	0.2202	likely_benign	0.2457	benign	-0.03	Destabilizing	0.959	D	0.453	neutral	N	0.44546391	None	None	N
H/R	0.099	likely_benign	0.1074	benign	-0.604	Destabilizing	0.008	N	0.313	neutral	N	0.370851508	None	None	N
H/S	0.3511	ambiguous	0.379	ambiguous	-0.144	Destabilizing	0.775	D	0.508	neutral	None	None	None	None	N
H/T	0.5101	ambiguous	0.5427	ambiguous	-0.037	Destabilizing	0.923	D	0.573	neutral	None	None	None	None	N
H/V	0.5024	ambiguous	0.5509	ambiguous	0.136	Stabilizing	0.923	D	0.689	prob.neutral	None	None	None	None	N
H/W	0.4693	ambiguous	0.5541	ambiguous	-0.007	Destabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
H/Y	0.1502	likely_benign	0.1716	benign	0.388	Stabilizing	0.941	D	0.48	neutral	N	0.516998722	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.