TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17973	54142;54143;54144	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
N2AB	16332	49219;49220;49221	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
N2A	15405	46438;46439;46440	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
N2B	8908	26947;26948;26949	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
Novex-1	9033	27322;27323;27324	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
Novex-2	9100	27523;27524;27525	chr2:178605260;178605259;178605258	chr2:179469987;179469986;179469985
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-114
• Domain position: 6
• Structural Position: 8
• Q(SASA): 0.458
• 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
G/A	rs2054500597	None	0.974	N	0.559	0.252	0.27855597813	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
G/A	rs2054500597	None	0.974	N	0.559	0.252	0.27855597813	gnomAD-4.0.0	2.03049E-06	None	None	None	None	N	None	3.49883E-05	0	None	0	0	None	0	0	0	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
G/A	0.25	likely_benign	0.2793	benign	-0.22	Destabilizing	0.974	D	0.559	neutral	N	0.497439887	None	None	N
G/C	0.6025	likely_pathogenic	0.6231	pathogenic	-0.964	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
G/D	0.6253	likely_pathogenic	0.6277	pathogenic	-0.464	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
G/E	0.6085	likely_pathogenic	0.6145	pathogenic	-0.611	Destabilizing	1.0	D	0.847	deleterious	N	0.496226378	None	None	N
G/F	0.8776	likely_pathogenic	0.8908	pathogenic	-0.917	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
G/H	0.7915	likely_pathogenic	0.8166	pathogenic	-0.377	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
G/I	0.7331	likely_pathogenic	0.768	pathogenic	-0.396	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
G/K	0.7956	likely_pathogenic	0.8362	pathogenic	-0.739	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/L	0.7735	likely_pathogenic	0.8032	pathogenic	-0.396	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
G/M	0.7703	likely_pathogenic	0.8023	pathogenic	-0.631	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
G/N	0.543	ambiguous	0.581	pathogenic	-0.454	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
G/P	0.9327	likely_pathogenic	0.9464	pathogenic	-0.309	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
G/Q	0.6817	likely_pathogenic	0.7121	pathogenic	-0.68	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
G/R	0.7393	likely_pathogenic	0.7718	pathogenic	-0.361	Destabilizing	1.0	D	0.876	deleterious	N	0.484977859	None	None	N
G/S	0.1893	likely_benign	0.208	benign	-0.604	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
G/T	0.3603	ambiguous	0.4106	ambiguous	-0.676	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/V	0.5602	ambiguous	0.6058	pathogenic	-0.309	Destabilizing	1.0	D	0.869	deleterious	D	0.52810951	None	None	N
G/W	0.7735	likely_pathogenic	0.7868	pathogenic	-1.064	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
G/Y	0.8034	likely_pathogenic	0.8275	pathogenic	-0.73	Destabilizing	1.0	D	0.89	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.