TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10090	30493;30494;30495	chr2:178702619;178702618;178702617	chr2:179567346;179567345;179567344
N2AB	9773	29542;29543;29544	chr2:178702619;178702618;178702617	chr2:179567346;179567345;179567344
N2A	8846	26761;26762;26763	chr2:178702619;178702618;178702617	chr2:179567346;179567345;179567344
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-86
• Domain position: 13
• Structural Position: 18
• Q(SASA): 0.5278
• 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/N	rs2075204317	None	0.061	None	0.143	0.146	0.218845423259	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
S/N	rs2075204317	None	0.061	None	0.143	0.146	0.218845423259	gnomAD-4.0.0	7.68494E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19625E-05	0	2.84349E-05

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	0.2091	likely_benign	0.229	benign	-0.495	Destabilizing	0.863	D	0.307	neutral	None	None	None	None	N
S/C	0.5279	ambiguous	0.5645	pathogenic	-0.405	Destabilizing	0.999	D	0.402	neutral	None	None	None	None	N
S/D	0.8272	likely_pathogenic	0.821	pathogenic	0.217	Stabilizing	0.884	D	0.231	neutral	None	None	None	None	N
S/E	0.8629	likely_pathogenic	0.8569	pathogenic	0.179	Stabilizing	0.939	D	0.233	neutral	None	None	None	None	N
S/F	0.8467	likely_pathogenic	0.8786	pathogenic	-0.751	Destabilizing	0.997	D	0.497	neutral	None	None	None	None	N
S/G	0.2897	likely_benign	0.3108	benign	-0.702	Destabilizing	0.826	D	0.281	neutral	None	None	None	None	N
S/H	0.7979	likely_pathogenic	0.7994	pathogenic	-1.161	Destabilizing	0.991	D	0.372	neutral	None	None	None	None	N
S/I	0.8054	likely_pathogenic	0.841	pathogenic	-0.066	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
S/K	0.952	likely_pathogenic	0.9502	pathogenic	-0.56	Destabilizing	0.759	D	0.253	neutral	None	None	None	None	N
S/L	0.4326	ambiguous	0.4955	ambiguous	-0.066	Destabilizing	0.939	D	0.405	neutral	None	None	None	None	N
S/M	0.6539	likely_pathogenic	0.6715	pathogenic	0.077	Stabilizing	0.997	D	0.365	neutral	None	None	None	None	N
S/N	0.4789	ambiguous	0.443	ambiguous	-0.388	Destabilizing	0.061	N	0.143	neutral	None	None	None	None	N
S/P	0.616	likely_pathogenic	0.6713	pathogenic	-0.175	Destabilizing	0.997	D	0.379	neutral	None	None	None	None	N
S/Q	0.8354	likely_pathogenic	0.8315	pathogenic	-0.564	Destabilizing	0.939	D	0.318	neutral	None	None	None	None	N
S/R	0.9174	likely_pathogenic	0.9263	pathogenic	-0.438	Destabilizing	0.015	N	0.21	neutral	None	None	None	None	N
S/T	0.2773	likely_benign	0.2783	benign	-0.476	Destabilizing	0.826	D	0.259	neutral	None	None	None	None	N
S/V	0.7684	likely_pathogenic	0.7974	pathogenic	-0.175	Destabilizing	0.991	D	0.467	neutral	None	None	None	None	N
S/W	0.8542	likely_pathogenic	0.8836	pathogenic	-0.721	Destabilizing	0.999	D	0.572	neutral	None	None	None	None	N
S/Y	0.7467	likely_pathogenic	0.7737	pathogenic	-0.457	Destabilizing	0.997	D	0.499	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.