ClinVar Miner

Submissions for variant NM_003001.5(SDHC):c.221C>T (p.Thr74Ile)

gnomAD frequency: 0.00001  dbSNP: rs1332910409
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000540277 SCV000641429 uncertain significance Gastrointestinal stromal tumor; Paragangliomas 3 2023-11-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 74 of the SDHC protein (p.Thr74Ile). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with SDHC-related conditions. ClinVar contains an entry for this variant (Variation ID: 465964). 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 expected to disrupt SDHC protein function with a positive predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002431621 SCV002727420 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-03 criteria provided, single submitter clinical testing The c.221C>T (p.T74I) alteration is located in exon 4 (coding exon 4) of the SDHC gene. This alteration results from a C to T substitution at nucleotide position 221, causing the threonine (T) at amino acid position 74 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV003105951 SCV003762095 uncertain significance not provided 2022-07-28 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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