TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8675	26248;26249;26250	chr2:178715163;178715162;178715161	chr2:179579890;179579889;179579888
N2AB	8358	25297;25298;25299	chr2:178715163;178715162;178715161	chr2:179579890;179579889;179579888
N2A	7431	22516;22517;22518	chr2:178715163;178715162;178715161	chr2:179579890;179579889;179579888
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-72
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.2407
• 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	rs868429008	-0.461	0.963	D	0.583	0.559	0.712839202888	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
S/F	rs868429008	-0.461	0.963	D	0.583	0.559	0.712839202888	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
S/F	rs868429008	-0.461	0.963	D	0.583	0.559	0.712839202888	gnomAD-4.0.0	2.56254E-06	None	None	None	None	N	None	3.38432E-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
S/A	0.071	likely_benign	0.0754	benign	-0.582	Destabilizing	0.001	N	0.199	neutral	D	0.527789797	None	None	N
S/C	0.1267	likely_benign	0.1393	benign	-0.304	Destabilizing	0.977	D	0.573	neutral	D	0.531556667	None	None	N
S/D	0.4819	ambiguous	0.5216	ambiguous	-0.47	Destabilizing	0.841	D	0.529	neutral	None	None	None	None	N
S/E	0.5422	ambiguous	0.5672	pathogenic	-0.389	Destabilizing	0.881	D	0.529	neutral	None	None	None	None	N
S/F	0.1351	likely_benign	0.1412	benign	-0.48	Destabilizing	0.963	D	0.583	neutral	D	0.523424128	None	None	N
S/G	0.1213	likely_benign	0.1263	benign	-0.915	Destabilizing	0.666	D	0.505	neutral	None	None	None	None	N
S/H	0.2806	likely_benign	0.2917	benign	-1.308	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
S/I	0.1027	likely_benign	0.1074	benign	0.22	Stabilizing	0.03	N	0.451	neutral	None	None	None	None	N
S/K	0.584	likely_pathogenic	0.5983	pathogenic	-0.552	Destabilizing	0.907	D	0.523	neutral	None	None	None	None	N
S/L	0.0703	likely_benign	0.0763	benign	0.22	Stabilizing	0.668	D	0.523	neutral	None	None	None	None	N
S/M	0.1399	likely_benign	0.1521	benign	0.263	Stabilizing	0.972	D	0.579	neutral	None	None	None	None	N
S/N	0.1334	likely_benign	0.1449	benign	-0.748	Destabilizing	0.383	N	0.547	neutral	None	None	None	None	N
S/P	0.8942	likely_pathogenic	0.8835	pathogenic	-0.011	Destabilizing	0.933	D	0.581	neutral	D	0.531049688	None	None	N
S/Q	0.421	ambiguous	0.441	ambiguous	-0.69	Destabilizing	0.995	D	0.577	neutral	None	None	None	None	N
S/R	0.5073	ambiguous	0.5093	ambiguous	-0.633	Destabilizing	0.986	D	0.581	neutral	None	None	None	None	N
S/T	0.0651	likely_benign	0.0684	benign	-0.615	Destabilizing	0.001	N	0.24	neutral	N	0.41325357	None	None	N
S/V	0.1083	likely_benign	0.1149	benign	-0.011	Destabilizing	0.047	N	0.403	neutral	None	None	None	None	N
S/W	0.3142	likely_benign	0.3099	benign	-0.619	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
S/Y	0.1587	likely_benign	0.1627	benign	-0.274	Destabilizing	0.981	D	0.582	neutral	D	0.532043611	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.