ClinVar Miner

Submissions for variant NM_000312.4(PROC):c.889G>C (p.Asp297His)

gnomAD frequency: 0.00013  dbSNP: rs199469471
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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 RCV000821496 SCV000962254 pathogenic Thrombophilia due to protein C deficiency, autosomal dominant 2024-03-29 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 297 of the PROC protein (p.Asp297His). This variant is present in population databases (rs199469471, gnomAD 0.04%). This missense change has been observed in individuals with protein C deficiency (PMID: 18573519, 24782131, 25393254, 25748729, 27517348). It has also been observed to segregate with disease in related individuals. This variant is also known as D255H. ClinVar contains an entry for this variant (Variation ID: 663591). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PROC protein function. Experimental studies have shown that this missense change affects PROC function (PMID: 21744130, 25393254, 25748729). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002487843 SCV002785405 pathogenic Thrombophilia due to protein C deficiency, autosomal recessive; Thrombophilia due to protein C deficiency, autosomal dominant 2024-01-04 criteria provided, single submitter clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc RCV002487843 SCV005415695 likely pathogenic Thrombophilia due to protein C deficiency, autosomal recessive; Thrombophilia due to protein C deficiency, autosomal dominant criteria provided, single submitter clinical testing PM2_Supporting+PM3+PP4+PP3_Moderate

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