ClinVar Miner

Submissions for variant NM_003244.4(TGIF1):c.83C>G (p.Ser28Cys)

gnomAD frequency: 0.00005  dbSNP: rs121909066
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000007394 SCV002301499 likely pathogenic Holoprosencephaly 4 2024-08-05 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 28 of the TGIF1 protein (p.Ser28Cys). This variant is present in population databases (rs121909066, gnomAD 0.006%). This missense change has been observed in individuals with holoprosencephaly (PMID: 10835638; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 6979). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt TGIF1 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects TGIF1 function (PMID: 10835638, 16962354). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Mendelics RCV002247257 SCV002516089 uncertain significance not specified 2022-05-04 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000007394 SCV003819488 uncertain significance Holoprosencephaly 4 2021-09-28 criteria provided, single submitter clinical testing
OMIM RCV000007394 SCV000027593 pathogenic Holoprosencephaly 4 2000-06-01 no assertion criteria provided literature only

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