TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8956	27091;27092;27093	chr2:178713268;178713267;178713266	chr2:179577995;179577994;179577993
N2AB	8639	26140;26141;26142	chr2:178713268;178713267;178713266	chr2:179577995;179577994;179577993
N2A	7712	23359;23360;23361	chr2:178713268;178713267;178713266	chr2:179577995;179577994;179577993
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: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-75
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4218
• 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/F	rs759580470	-0.824	0.006	D	0.307	0.291	0.576973211123	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.05E-06	0
S/F	rs759580470	-0.824	0.006	D	0.307	0.291	0.576973211123	gnomAD-4.0.0	1.59735E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86822E-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	0.0813	likely_benign	0.0826	benign	-0.374	Destabilizing	0.01	N	0.133	neutral	N	0.479611848	None	None	N
S/C	0.1626	likely_benign	0.1688	benign	-0.384	Destabilizing	0.975	D	0.484	neutral	N	0.497434844	None	None	N
S/D	0.3974	ambiguous	0.4402	ambiguous	0.31	Stabilizing	0.828	D	0.331	neutral	None	None	None	None	N
S/E	0.4438	ambiguous	0.4737	ambiguous	0.241	Stabilizing	0.704	D	0.307	neutral	None	None	None	None	N
S/F	0.1522	likely_benign	0.1592	benign	-0.943	Destabilizing	0.006	N	0.307	neutral	D	0.526616361	None	None	N
S/G	0.1438	likely_benign	0.1503	benign	-0.509	Destabilizing	0.495	N	0.321	neutral	None	None	None	None	N
S/H	0.2942	likely_benign	0.2882	benign	-1.003	Destabilizing	0.981	D	0.492	neutral	None	None	None	None	N
S/I	0.1541	likely_benign	0.1583	benign	-0.146	Destabilizing	0.543	D	0.449	neutral	None	None	None	None	N
S/K	0.5101	ambiguous	0.5421	ambiguous	-0.41	Destabilizing	0.543	D	0.31	neutral	None	None	None	None	N
S/L	0.0863	likely_benign	0.0867	benign	-0.146	Destabilizing	0.003	N	0.243	neutral	None	None	None	None	N
S/M	0.1672	likely_benign	0.1657	benign	-0.034	Destabilizing	0.893	D	0.503	neutral	None	None	None	None	N
S/N	0.1662	likely_benign	0.1791	benign	-0.274	Destabilizing	0.828	D	0.321	neutral	None	None	None	None	N
S/P	0.7006	likely_pathogenic	0.7799	pathogenic	-0.192	Destabilizing	0.927	D	0.574	neutral	N	0.490179916	None	None	N
S/Q	0.4253	ambiguous	0.4317	ambiguous	-0.441	Destabilizing	0.893	D	0.45	neutral	None	None	None	None	N
S/R	0.4182	ambiguous	0.4333	ambiguous	-0.282	Destabilizing	0.007	N	0.252	neutral	None	None	None	None	N
S/T	0.0654	likely_benign	0.0671	benign	-0.345	Destabilizing	0.01	N	0.117	neutral	N	0.423526492	None	None	N
S/V	0.1502	likely_benign	0.1539	benign	-0.192	Destabilizing	0.329	N	0.401	neutral	None	None	None	None	N
S/W	0.3011	likely_benign	0.3207	benign	-0.967	Destabilizing	0.995	D	0.518	neutral	None	None	None	None	N
S/Y	0.1593	likely_benign	0.166	benign	-0.66	Destabilizing	0.759	D	0.571	neutral	N	0.515668649	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.